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1.
BMC Pulm Med ; 19(1): 262, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878900

RESUMO

BACKGROUND: Our study aimed to verify the prognostic value of circulating tumor cells (CTCs) prior to initial treatment on survival of non-small cell lung cancer (NSCLC) by using meta-analysis and system review of published studies. MATERIALS AND METHODS: The PubMed, EMBASE and Cochrane Library were searched, respectively, to identify all studies that addressed the issues of CTCs prior to initial treatment and progression-free survival (PFS) and overall survival (OS). Finally, ten citations were included for analysis and assessment of publication bias by using review manager 5.3 statistical software and STATA 15.0. RESULTS: Randomized model analyzing multivariate Cox Proportional Hazards Regression indicated that higher abundance of CTCs significantly predicts poorer prognosis of lung cancer cases basing both on PFS (Z = 2.31, P = 0.02) and OS of advanced cases (Z = 2.44, P = 0.01), and systematic study aslo indicated the similar results. CONCLUSION: High CTCs prior to initial treatment can predict shorter PFS and OS in NSCLC, and further studies are warranted in the future.

2.
World J Surg Oncol ; 17(1): 158, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506081

RESUMO

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPLs) is a challenging task for pulmonologists, especially for small PPLs. Conventional localization of these small PPLs, which are > 1 cm away from the visceral pleura in operation, is quite difficult. Currently used methods inevitably damage the visceral pleura and may cause a series of complications, such as pneumothorax and hemothorax. Hence, the present study aimed to find out an intraoperative localization method with no damage to the visceral pleura. METHODS: We retrospectively reviewed 21 patients with PLLs who underwent electromagnetic navigation bronchoscopy (ENB)-guided biopsy plus a new methylene blue staining with the help of massage (Massage Staining) in our department between August 2017 and December 2018. RESULTS: The median age of these 21 patients was 51.3 ± 2.1 years. The diameter of the PPLs was 8.2 ± 2.3 mm. The rate of successful biopsy was 76.2%, and the rate of excellent or satisfactory of Massage Staining was 81.0%, while all lesions of these 21 cases were included in the range of staining, and the median distance from the edge of the stained site to the edge of the lesion was 29 ± 18 mm. The duration of ENB-guided biopsy plus Massage Staining was 26.7 ± 5.3 min, and the intraoperative blood loss was 3.3 ± 1.5 ml. No pneumothorax, hemorrhage, and tracheal injury occurred intraoperatively. CONCLUSIONS: The ENB-guided biopsy combined with Massage Staining is an innovative one-stop strategy designed to enhance the precision of thoracic surgery. The Massage Staining avoids damage to the visceral pleura, causes the low incidence of complications, but yields precise localization of PPLs.

3.
J Exp Clin Cancer Res ; 38(1): 165, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30987652

RESUMO

BACKGROUND: miRNAs play crucial role in the progression of K-Ras-mutated nonsmall cell lung cancer (NSCLC). However, most studies have focused on miRNAs that target K-Ras. Here, we investigated miRNAs regulated by mutant K-Ras and their functions. METHODS: miRNAs regulated by mutant K-Ras were screened using miRNA arrays. miR-199b expression levels were measured by qRT-PCR. The protein expression levels were measured using Western blot and immunohistochemistry. The effects of miR-199b on NSCLC were examined both in vitro and in vivo by overexpressing or inhibiting miR-199b. DNA methylation was measured by bisulfite sequencing. RESULTS: An inverse correlation was observed between K-Ras mutation status and miR-199b levels in NSCLC specimens and cell lines. The inhibition of miR-199b stimulated NSCLC growth and metastasis, while restoration of miR-199b suppressed K-Ras mutation-driven lung tumorigenesis as well as K-Ras-mutated NSCLC growth and metastasis. miR-199b inactivated ERK and Akt pathways by targeting K-Ras, KSR2, PIK3R1, Akt1, and Rheb1. Furthermore, we determined that mutant K-Ras inhibits miR-199b expression by increasing miR-199b promoter methylation. CONCLUSION: Our findings suggest that mutant K-Ras plays an oncogenic role through downregulating miR-199b in NSCLC and that overexpression of miR-199b is a novel strategy for the treatment of K-Ras-mutated NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Metilação de DNA , Progressão da Doença , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Humanos , Neoplasias Pulmonares/patologia , Modelos Moleculares , Mutação , Proteínas Proto-Oncogênicas c-akt/metabolismo
4.
BMC Pulm Med ; 18(1): 146, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30176840

RESUMO

BACKGROUND: Convenient approaches for accurate biopsy are extremely important to the diagnosis of lung cancer. We aimed to systematically review the clinical updates and development trends of approaches for biopsy, i.e., CT-guided PTNB (Percutaneous Transthoracic Needle Biopsy), ENB (Electromagnetic Navigation Bronchoscopy), EBUS-TBNA (Endobroncheal Ultrasonography-Transbronchial Needle Aspiration), mediastinoscopy and CTC (Circulating Tumor Cell). METHODS: Medline and manual searches were performed. We identified the relevant studies, assessed study eligibility, evaluated methodological quality, and summarized diagnostic yields and complications regarding CT-guided PTNB (22 citations), ENB(31 citations), EBUS-TBNA(66 citations), Mediastinoscopy(15 citations) and CTC (19 citations), respectively. RESULTS: The overall sensitivity and specificity of CT-guided PTNB were reported to be 92.52% ± 3.14% and 97.98% ± 3.28%, respectively. The top two complications of CT-guided PTNB was pneumothorax (946/4170:22.69%) and hemorrhage (138/1949:7.08%). The detection rate of lung cancer by ENB increased gradually to 79.79% ± 15.34% with pneumothorax as the top one complication (86/1648:5.2%). Detection rate of EBUS-TBNA was 86.06% ± 9.70% with the top three complications, i.e., hemorrhage (53/8662:0.61%), pneumothorax (46/12432:0.37%) and infection (34/11250:0.30%). The detection rate of mediastinoscopy gradually increased to 92.77% ± 3.99% with .hoarseness as the refractory complication (4/2137:0.19%). Sensitivity and specificity of CTCs detection by using PCR (Polymerase Chain Reaction) were reported to be 78.81% ± 14.72% and 90.88% ± 0.53%, respectively. CONCLUSION: The biopsy approaches should be chosen considering a variety of location and situation of lesions. CT-guided PTNB is effective to reach lung parenchyma, however, diagnostic accuracy and incidence of complications may be impacted by lesion size or needle path length. ENB has an advantage for biopsy of smaller and deeper lesions in lung parenchyma. ENB plus EBUS imaging can further improve the detection rate of lesion in lung parenchyma. EBUS-TBNA is relatively safer and mediastinoscopy provides more tissue acquisition and better diagnostic yield of 4R and 7th lymph node. CTC detection can be considered for adjuvant diagnosis.


Assuntos
Biópsia Guiada por Imagem/métodos , Neoplasias Pulmonares/diagnóstico , Pulmão/patologia , Mediastino/patologia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Sensibilidade e Especificidade
5.
J Cardiothorac Surg ; 13(1): 54, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29859106

RESUMO

BACKGROUND: Compensatory hyperhidrosis (CH) is a frequent side effect after sympathectomy for the treatment of primary palmar hyperhidrosis. We determined the effects of demographic and clinical factors which may increase the duration of CH (DCH). METHODS: One hundred twenty-two patients who had undergone sympathectomies from 2014 to 2016 were retrospectively reviewed. Anxiety was evaluated using the State and Trait Anxiety Inventory score. Follow-up evaluations continued until CH remitted. A Cox proportional hazards model was used to determine the association between DCH and variables. RESULTS: DCH ranged from 5 to 27 weeks (median, 11.47 weeks). Severe CH (HR = 0.318, 95% CI, 0.136-0.741) and exacerbated anxiety 1 month post-operatively (HR = 0.816, 95% CI, 0.746-0.893) may prolong CH. A positive correlation between post-operative anxiety and DCH was common in patients with moderate or severe CH, and in cases with forearm CH. CONCLUSIONS: Pre- and post-operative anxiety should be evaluated, and anti-anxiety treatment is offered to patients with moderate-to-severe CH to shorten the DCH.


Assuntos
Ansiedade/etiologia , Hiperidrose/cirurgia , Complicações Pós-Operatórias , Simpatectomia/psicologia , Adulto , Ansiedade/diagnóstico , Feminino , Seguimentos , Humanos , Hiperidrose/psicologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Mol Ther Nucleic Acids ; 9: 145-154, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246293

RESUMO

Dysregulated miRNAs play important role in K-ras mutation or smoking caused lung tumorigenesis. Here, we investigate the role and mechanism of miR-124 in K-ras mutation or smoking-caused lung tumorigenesis and evaluate the therapeutic potential of miR-124 agomiR in K-ras mutation or smoking-caused lung cancer treatment. Our data show that smoking suppresses miR-124 expression, and decreased miR-124 expression is inversely correlated with the p-Akt level and predicts poor overall survival in non-small-cell lung cancer (NSCLC) patients. The overexpression of miR-124 suppressed NSCLC growth by inhibiting the Akt pathway by targeting Akt1 and Akt2. In addition, the systemic delivery of miR-124 agomiR dramatically suppressed tumorigenesis in both NNK-induced lung cancer model and K-rasLA1 transgenic mice by increasing apoptosis and inhibiting cell proliferation. Our findings suggest that smoking inhibits the expression of miR-124, and decreased miR-124 contributes to Akt activation, thereby promoting NSCLC progression. Our findings also represent a novel potential therapeutic strategy for lung cancer.

7.
Mol Ther Nucleic Acids ; 8: 111-122, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28918013

RESUMO

Cancer stem cells (CSCs) play an important role in osteosarcoma (OS) metastasis and recurrence, and both Wnt/ß-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/ß-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/ß-catenin and Notch signaling. The overexpression of miR-135b simultaneously targets multiple negative regulators of the Wnt/ß-catenin and Notch signaling pathways, including glycogen synthase kinase-3 beta (GSK3ß), casein kinase 1a (CK1α), and ten-eleven translocation 3 (TET3). Therefore, upregulated miR-135b promotes CSC traits, lung metastasis, and tumor recurrence in OS. Notably, antagonizing miR-135b potently inhibits OS lung metastasis, cancer cell stemness, CSC-induced tumor formation, and recurrence in xenograft animal models. These findings suggest that miR-135b mediates the constitutive activation of Wnt/ß-catenin and Notch signaling, and that the inhibition of miR-135b is a novel strategy to inhibit tumor metastasis and prevent CSC-induced recurrence in OS.

8.
World J Surg Oncol ; 15(1): 150, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28789662

RESUMO

BACKGROUND: Thymectomy is the primary approach for the treatment of myasthenia gravis (MG). This retrospective study aimed to identify the clinical and demographical features that may impact the duration of mechanical ventilation (DMV), the long-term survival, and the quality of life (QOL) in patients with post-thymectomy myasthenic crisis (PTMC). METHODS: We reviewed the patients who suffered from PTMC from June 2008 to November 2015. Cox proportional hazard regression analysis was used to identify potential prognostic factors that may impact DMV and long-term survival. Spearman bivariate correlation analysis was used to analyze the relationship between DMV and QOL. Statistical powers were calculated. RESULTS: In total, 70 patients with PTMC were enrolled. Alcohol abuse, high scores of Myasthenia Gravis Foundation of America (MGFA) classification and Clavien-Dindo classification were critical factors that remarkably delayed early extubation. High scores of Osserman's classification, MGFA classification, and Clavien-Dindo classification predicted a poor prognosis in PTMC patients. Occupational skills and job status were observed to be negatively affected in PTMC patients. CONCLUSIONS: To decrease the duration of mechanical ventilation, we suggest alcohol abstinence before the operation, appropriate preoperative treatment to decrease MGFA classification, and greater attention to the treatment of postoperative complications.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Miastenia Gravis/cirurgia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Respiração Artificial/estatística & dados numéricos , Timectomia/efeitos adversos , Adulto , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/mortalidade , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/métodos , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
Am J Transl Res ; 9(7): 3282-3292, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28804546

RESUMO

High levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in esophageal squamous carcinoma. C-C chemokine receptor type 7 (CCR7) is overexpressed in multiple tumor types and has been suggested to act as an oncogene and pro-angiogenic factor. This study aimed to elucidate the effect of CCR7 on the angiogenic capacity of esophageal squamous carcinoma cells in vitro. Expression of CCR7 in esophageal squamous carcinoma cell lines and normal human esophageal epithelial cell line was examined by western blotting and quantitative real-time PCR. CCR7 was stably overexpressed or transiently knocked down in esophageal squamous carcinoma cell lines. Overexpressing CCR7 enhanced the capacity of esophageal squamous carcinoma cell conditioned media to induce human umbilical vein endothelial cells (HUVEC) proliferation and migration and neovascularization in the chicken chorioallantoic membrane (CAM) assay. While silencing CCR7 caused an opposite outcome. Moreover, we demonstrated that CCR7 activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and regulated its targets, including vascular endothelial growth factor A (VEGF-A), VEGF-C, tumor necrosis factor-α (TNFα), interleukin (IL)-6, IL-8 and transforming growth factor-ß (TGF-ß) expression. Additionally, CCR7 down-regulation reduced tumor volume and weight in xenograft mouse model, and significantly decreased NF-κB signaling pathway. This study suggests that CCR7 plays an important pro-angiogenic role in esophageal squamous carcinoma via a mechanism linked to activation of the NF-κB pathway; CCR7 may represent a potential target for anti-angiogenic therapy in esophageal squamous carcinoma.

10.
Am J Transl Res ; 9(6): 2684-2693, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28670361

RESUMO

OBJECTIVE: This study aimed to investigate the effect of Sox3 expression on biological behaviors of esophageal squamous cell carcinoma (ESCC) and explore its possible mechanism. METHODS: ESCC cell lines that highly expressed Sox3 were selected and transfected with lentivirus carrying sox3 siRNA to establish ESCC cell lines which expressed Sox3 of different levels. Using in vitro experiments including cell invasion, cell scratch, cell proliferation and tube formation of lymphatic endothelial cells, as well as an in vivo experiment of axillary lymph node metastasis in a nude mouse model of a xenotransplanted tumor, the effect of Sox3 expression variation on lymphangiogenesis and lymph node metastasis in ESCC cells was investigated. In addition, ELISA, Western blot and immunohistochemical methods were used to study the regulatory effects of Sox3 on relevant molecules such as VEGF-C/D and to explore the potential mechanisms that affected lymphatic metastasis. RESULTS: The high expression of Sox3 in ESCC cells in vitro could significantly promote the proliferation, invasion, migration and tube formation of lymphatic endothelial cells. High expression of Sox3 in vivo could significantly promote lymph node metastasis of ESCC cells, and we have demonstrated that the upregulation of Sox-3 expression could promote the expression and secretion of VEGF-C and VEGF-D both in vivo and in vitro. After blocking the VEGFR-3 receptors on lymphatic endothelial cells, the effect of Sox3 on promoting lymphangiogenesis has decreased significantly, confirming that Sox3 acts through VEGF-C/D to promote lymphangiogenesis. CONCLUSIONS: It is suggested that Sox3 possibly induces lymphangiogenesis by increasing the expression of VEGF-C/D in ESCC cells, thereby promoting the lymph node metastasis of the tumor. Thus, Sox-3 may become a new prognostic marker and therapeutic target in ESCC.

11.
Oncotarget ; 8(14): 23130-23141, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28423562

RESUMO

PURPOSE: The study aimed to monitor circulating tumor cells (CTCs) in early stage lung adenocarcinoma patients. RESULTS: CTCs were characterized and classified to epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-) CTCs, as per epithelial-mesenchymal transition(EMT) biomarkers. CTCs could not be found in healthy controls. However, in cohort A, CTCs were found in 17 (17/18) cases. Detection rate of E-CTCs was lower (5/18) compared with M-CTC (10/18) or E&M-CTC (14/18). Highly abundant M-CTCs were prone to being in the tumors > 2 cm. In cohorts A and B, CTCs count increased significantly in all patients with tumor progression (7/7). Higher CTCs level or change range could be found postoperatively in the patients with tumor progression, as compared with patients with disease free survival (P < 0.01). Additionally, CTCs detected by CanPatrolTM could be validated by CytoploRare or Pep@MNPs. MATERIALS AND METHODS: We included four cohorts of patients and 20 healthy controls. In cohort A, CTCs were detected by a newly established approach, i.e., CanPatrolTM, prior to anesthesia and monitored after operation longitudinally. In cohort B, CTCs were not assessed prior to operation, but were longitudinally detected after operation. For validation, we detected FOLR(+)-CTCs by using CytoploRare and EPCAM(+)-CTCs by using Pep@MNPs prior to operation, in cohorts C and D, respectively. CONCLUSION: CTCs can be detected in early stage lung adenocarcinoma, even in adenocarcinoma in situ, and CTCs detection can effectively monitor tumor progression. The distinguishing of biomarkers of highly invasive and aggressive CTCs warrants further robust study.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/patologia , Adenocarcinoma de Pulmão , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
12.
World J Surg ; 41(8): 2039-2045, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28289835

RESUMO

BACKGROUND: The aim of this meta-analysis and systematic review of published evidence was to optimize chest tube management for fast-track rehabilitation of lung cancer patients after video-assisted thoracic surgery (VATS). METHODS: The PubMed, Web of Science, and EMBASE databases were searched to identify all studies that addressed the issue of chest tube management after VATS for lung cancer. Finally, 35 articles were included for analysis, i.e., 29 randomized controlled trials and 6 clinical trials. RESULTS: After synthesis of the published evidence, the following protocol for chest tube drainage was formulated: (1) after VATS lung wedge resection, chest tube drainage can be omitted in selected cases; (2) normally, one 28Fr chest tube (or 19Fr Blake drain) is placed; (3) the use of a digital monitoring system is recommended; (4) in case of increasing pneumothorax or severe air leakage supported by digital recording system, the tube should be placed with active suction; and (5) the chest tube can be removed within 48 h postoperatively when air leakage is resolved and fluid drainage is <400 mL/day. CONCLUSIONS: Further multicenter studies are warranted based on the variations of body sizes among different ethnicities.


Assuntos
Tubos Torácicos , Neoplasias Pulmonares/reabilitação , Neoplasias Pulmonares/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Drenagem/métodos , Humanos , Tempo de Internação , Cicatrização
13.
Surg Endosc ; 31(9): 3475-3482, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27924395

RESUMO

BACKGROUND: Minimally invasive esophagectomy (MIE) has been shown to be a feasible technique for the treatment of esophageal cancer; however, its postoperative morbidity remains high. This retrospective study aimed to evaluate the effect of postoperative complications on long-term outcomes in patients who have undergone MIE for esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study enrolled patients who had undergone MIE for ESCC between September 2009 and November 2014; all procedures were performed by a single surgical team. Relevant patient characteristics and postoperative variables were collected and evaluated. The disease-free survival (DFS) and disease-specific survival (DSS) were determined by the Kaplan-Meier method, and compared by log-rank tests. Possible predictors of survival were subjected to univariate analysis and multivariate Cox proportional hazard regression analysis. RESULTS: In all, data on 214 patients with ESCC were analyzed, including 170 men and 44 women. All study subjects had undergone thoracoscopic or thoracoscopic-laparoscopic esophagectomy and cervical esophagogastric anastomosis. One hundred and thirty patients (60.7%) had postoperative complications (Grades 1-4). The overall DFS and DSS rates were 80.0 and 88.9% at 1 year, 48.6 and 54.2% at 3 years, and 43.2 and 43.5% at 5 years, respectively. Univariate analysis and multivariate Cox proportional hazard regression analysis showed that T stage, N stage, and tumor grade were independent prognostic factors for long-term survival; however, postoperative complications had no significant effect on the DFS or DSS of this patient cohort (log-rank test, p = 0.354 and 0.160, respectively). CONCLUSIONS: Postoperative complications have no significant effect on long-term survival in patients who have undergone MIE for ESCC.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Laparoscopia , Complicações Pós-Operatórias/mortalidade , Toracoscopia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Oncol Lett ; 8(1): 454-460, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24959295

RESUMO

In lung cancer A549 cells, the present study evaluated the associations between p130cas expression and the activation of p38 or Smad2, which are components of two of the main signaling pathways of transforming growth factor-ß1 (TGF-ß1), i.e., epithelial-mesenchymal transition (EMT) and apoptosis, respectively. TGF-ß1-induced EMT was investigated by inspecting cell shape and cell migration, and by testing E-Cadherin, N-Cadherin and Vimentin biomarkers in p130cas-RNA interference (RNAi)-A549 cells. The changes in TGF-ß1-induced apoptosis, i.e., cleaved Caspase-3 levels, were additionally analyzed following p130cas-RNAi. p130cas-knockdown decreased the phosphorylated (p)-p38 expression level, and blockaded the TGF-ß1-induced activation of p-p38 in the A549 cells. p130cas-knockdown arrested cell migration and impaired TGF-ß1-induced EMT in the A549 cells, characterized by changes in cell morphology and biomarker levels. However, p130cas-knockdown had no impact on the activation of Smad2 and the cleavage of Caspase-3. These results indicate that p130cas is a novel molecular 'rheostat' that alters the function of the TGF-ß1 signaling pathway from tumor suppression to tumor promotion in lung cancer cells. The underlying mechanism warrants further study.

15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 44(1): 80-3, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23600216

RESUMO

OBJECTIVE: To determine the correlation between in vitro release and in vivo absorption of sustained-releasing tablets of neostigmine bromide. METHODS: Water was used as dissolution medium to measured in vitro release of neostigmine bromide. After a single oral administration of 100 mg neostigmine bromide to rabbits, the plasma concentrations of neostigmine bromide in the rabbits were determined by HPLC. The compartment model and deconvolution method were employed to explain the in vitro-in vivo correlation. RESULTS: Using Y as cumulative in vitro release and Fa as percentage of absorption, the regression equation was established: Fa = 0.9298Y + 4.6074, r = 0.9961. The input function of R = 2.0163Y-11.242,r = 0.9270. CONCLUSION: The correlation between in vitro release and in vivo absorption of neostigmine bromide is good.


Assuntos
Neostigmina/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Preparações de Ação Retardada/farmacocinética , Coelhos , Solubilidade , Comprimidos
16.
Surg Today ; 43(6): 690-3, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23139047

RESUMO

We report a case of pulmonary adenofibroma, a rare benign soft-tissue tumor characterized by a combination of glandular and spindle stromal elements, in a 55-year-old man. This case is interesting because of the unusual X-ray and computed tomography (CT) imaging findings of a well-defined, subpleural soft-tissue nodule in the inferior lobe of the left lung, which showed no enhancement after contrast scan. The tumor was resected completely via video-assisted thoracoscopy. Microscopic and immunohistochemical examinations supported the diagnosis of a benign pulmonary adenofibroma. The patient remains well with no evidence of recurrence 16 months after surgery. Although the imaging findings were nonspecific, adenofibroma may be one of diagnostic inclusions of soft-tissue nodules of the lung in middle-aged patients.


Assuntos
Adenofibroma/diagnóstico , Adenofibroma/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Adenofibroma/patologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Int J Nanomedicine ; 7: 3929-38, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22915844

RESUMO

OBJECTIVE: Previous studies on various enzymosomes (functional lipid vesicles encapsulating an enzyme) have been mostly carried out in vitro and have focused on preserving catalytic activity and improving the stability of the enzyme. Until now, few studies have focused on their in vivo fate. Similarly, although we have previously reported the increased in vitro uricolytic activity (about 2.2 times higher than that of free uricase, or three times higher than that of PEGylated uricase, Puricase(®), under physiological pH and temperature) and improved stability of the novel alkaline enzymosomes (functional lipid vesicles encapsulating uricase from Candida utilis: uricase-containing lipid vesicles, UOXLVs), it is still necessary to study the biological properties and hypouricemic effects of UOXLVs in vivo. METHODS: The enzyme kinetics, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary safety of UOXLVs were evaluated. RESULTS: The Michaelis constant (K(m)) value of the UOXLVs was slightly lower than that of the free enzyme. The enzyme release from the UOXLVs lasted over 12 hours and their circulation half-life was about sevenfold longer than that of the free uricase. Meanwhile, the UOXLVs had a 22-fold increase in the area under the curve compared with the free uricase. Furthermore, it took less than 3 hours for the UOXLVs to lower the plasma uric acid concentration from a high to a normal level, compared with 6 hours for the free uricase. In addition, the UOXLVs had much less immunogenicity than free uricase and were well tolerated by all animals throughout the observation period. CONCLUSION: The UOXLVs markedly improved the biological properties and enhanced the hypouricemic effects of uricase in vivo.


Assuntos
Candida/enzimologia , Portadores de Fármacos/química , Urato Oxidase/química , Ácido Úrico/metabolismo , Alantoína/sangue , Alantoína/metabolismo , Animais , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Estabilidade Enzimática , Hemólise/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Cinética , Masculino , Ratos , Ratos Sprague-Dawley , Urato Oxidase/metabolismo , Urato Oxidase/farmacologia , Ácido Úrico/sangue
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 43(3): 458-61, 477, 2012 May.
Artigo em Chinês | MEDLINE | ID: mdl-22812258

RESUMO

OBJECTIVE: To prepare orally disintegrating tablets containing pyridostigmine bromide and optimize formulations. METHODS: Solid dispersion was prepared using solvent evaporation-deposition method. The formulation was optimized by central composite design-response surface methodology (RSM plus CCD) with disintegration time as a reference parameter. RESULTS: The orally disintegrating tablets showed integrity and were smooth with desirable taste and feel in mouth. The disintegration time was less than 30 s. The cumulative drug dissolution was around 8.5% (around 2.5 mg which was less than bitterness threshold of pyridostigmine bromide of 3 mg) within 5 min in water while the cumulative drug dissolution was higher than 95% within 2 min in 0.1 N HCl. CONCLUSION: The orally disintegrating tablets are reasonable in formulation, feasible in technology and patient-friendly.


Assuntos
Inibidores da Colinesterase/administração & dosagem , Brometo de Piridostigmina/administração & dosagem , Administração Bucal , Química Farmacêutica , Feminino , Humanos , Masculino , Controle de Qualidade , Comprimidos/administração & dosagem , Paladar
19.
PLoS One ; 7(4): e36124, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22558353

RESUMO

OBJECTIVE: Our previous study suggested the potential clinical implications of BCAR1 in non-small-cell lung cancer (NSCLC) (Mol Diagn Ther. 2011. 15(1): 31-40). Herein, we aim to evaluate the predictive power of BCAR1 as a marker for poor prognosis in NSCLC cases, verify the carcinogenic roles of BCAR1 in the A549 lung adenocarcinoma cell line, and testify to the BCAR1/phospho-p38 axis. METHODS: Between January 2006 and June 2010, there were a total of 182 patients with NSCLC (151 cases with available follow up data, and 31 cases lost to follow-up due to the invalid contact information). We inspected BCAR1, phospho-BCAR1(Tyr410), phospho-p38(Thr180/Tyr182) and p38 expression in NSCLC tissues and matched adjacent normal tissues by immunoblotting and IHC. After BCAR1 -RNA interference in A549 cells, we inspected the protein expression (BCAR1, phospho-BCAR1, phospho-p38 and p38) and performed cell biology experiments (cell growth, migration and cycle). RESULTS: BCAR1 was overexpressed in NSCLC tissues (177/182) and cell lines (A549 and Calu-3). However, it was not detected in the normal adjacent tissue in 161 of the 182 cases. Higher BCAR1 levels were strongly associated with more poorly differentiated NSCLC and predicted poorer prognosis. BCAR1 knockdown caused cell growth arrest, cell migration inhibition and cell cycle arrest of A549 cells. Overexpression of BCAR1 was associated with activation of p38 in NSCLC cases, and BCAR1 knockdown caused reduction of phospho-p38 levels in A549 cells. CONCLUSION: Overexpression of BCAR1 is a predictor of poor prognosis in NSCLC and plays important carcinogenic roles in carcinogenesis, probably via activation of p38 MAPK. However, further investigations are required immediately.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Transformação Celular Neoplásica/metabolismo , Proteína Substrato Associada a Crk/metabolismo , Neoplasias Pulmonares/metabolismo , Idoso , Apoptose , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/patologia , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fosforilação , Prognóstico , Análise de Regressão , Análise de Sobrevida , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Arch Pharm Res ; 35(3): 499-508, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22477197

RESUMO

A novel pyridostigmine bromide (PB)-phospholipid nanocomplex (PBPLC) was prepared to increase the bioavailability of PB. A central composite design approach was employed for process optimization. The physicochemical properties of PBPLC were investigated by means of differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy and the n-octano/water partition coefficient. The intestinal permeability of PBPLC was observed via a single pass intestinal perfusion in rats. After oral administration of PBPLC, the concentrations of PB at predetermined time points were determined by HPLC, and the pharmacokinetic parameters were computed by DAS 2.1.1 software. Multiple linear regression analysis for process optimization revealed that the optimal PBPLC was obtained when the values of X(1), X(2), and X(3) were 8, 40°C, and 4 mg/mL, respectively. The average particle size and zeta potential of PBPLC with the optimized formulation were 204.60 nm and -25.12 mV, respectively. Non-covalent interactions between PB and phospholipids were found in the PBPLC. The n-octanol/water partition coefficient of PBPLC was substantially increased. PBPLC had better intestinal permeability in comparison with free PB. Mean plasma drug concentration-time curves of PBPLC and free PB after oral administration were both in accordance with the two-compartment open model. The values of pharmacokinetic parameters of PBPLC and free PB were the peak time (T(max)) 2 h vs 2 h, the maximum concentration (C(max)) 22.79 µg/mL vs 6.00 µg/mL, and the value of the area under the concentration vs time curve (AUC(0-∞)) 7128.21 µg·min/mL vs 1772.36 µg·min/mL, respectively. In conclusion, compared with free PB, PBPLC remarkably improves the oral bioavailability of PB, which is likely due to its higher lipophilicity and permeability.


Assuntos
Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/farmacocinética , Nanopartículas , Fosfolipídeos/química , Brometo de Piridostigmina/administração & dosagem , Brometo de Piridostigmina/farmacocinética , 1-Octanol/química , Administração Oral , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Química Farmacêutica , Inibidores da Colinesterase/sangue , Inibidores da Colinesterase/química , Composição de Medicamentos , Absorção Intestinal , Mucosa Intestinal/metabolismo , Modelos Lineares , Masculino , Modelos Biológicos , Nanotecnologia , Permeabilidade , Brometo de Piridostigmina/sangue , Brometo de Piridostigmina/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Solventes/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Tecnologia Farmacêutica/métodos , Água/química
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