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Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.
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Insuficiência Cardíaca , Sistema de Sinalização das MAP Quinases , Animais , Ratos , Transdução de Sinais , Insuficiência Cardíaca/tratamento farmacológico , Comprimidos , Cardiomegalia/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por MitógenoRESUMO
BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. FINDINGS: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. INTERPRETATION: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature. FUNDING: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Vimblastina/análogos & derivados , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , China , Cisplatino/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina , Adulto JovemRESUMO
Objectives Pulmonary sequestration is a rare developmental abnormality of the lower respiratory system. This study aimed to evaluate the effectiveness of wedge resection compared with lobectomy for the treatment of intralobar pulmonary sequestration. Methods Video-assisted thoracic surgery (VATS) for intralobar pulmonary sequestration was performed in 26 patients in our institute between December 2006 and January 2015. Data regarding patient demographics, major complaints, diagnostic procedures, operative treatment, and treatment outcome were retrospectively analyzed. Results VATS was performed successfully in all patients. Wedge resection was performed in 7 patients and lobectomy in 19 patients. Conversion to thoracotomy was not required in any case. Statistical analysis revealed that operation duration and blood loss with wedge resection were significantly less than with lobectomy (p = 0.032 and 0.014, respectively). No significant differences were found in the mean drainage time, postoperative length of hospital stay, or complications. During our long-term follow-up, no patients had chronic cough, bloody sputum, or pneumonia. Conclusion VATS for intralobar pulmonary sequestration is feasible and safe. Lobectomy is the generally accepted operative method. However, wedge resection is a feasible alternative to lobectomy in select cases.
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Sequestro Broncopulmonar/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida , Adolescente , Adulto , Idoso , Biópsia , Perda Sanguínea Cirúrgica , Sequestro Broncopulmonar/diagnóstico por imagem , Drenagem , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Terapêutica , Cirurgia Torácica Vídeoassistida/efeitos adversos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: To investigate the mechanisms of lung adenocarcinoma cell metastasis and provide a theoretical basis for the in-depth study of lung adenocarcinoma. METHODS: A549 cells are incubated with different concentrations of Furin inhibitor for indicated times. The proliferation and migration were confirmed with MTT, colony formation, wound Healing and Transwell assayes. Hochest 33342 / PI double staining was used to detect apoptosis. Cell migration and apoptosis associated proteins were analysed by enzyme-linked immunosorbent assay (ELISA) and western blot. RESULTS: We have found that Furin inhibitor play a significant role in inhibition A549 cell growth. And we also found cell migration was inhibited significantly upon Furin inhibitor treatment. CONCLUSION: The proliferration and migration of A549 cell were inhibited by Furin inbitor through down-regulation the expression of migration and apoptosis related proteins.
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Objective: Genotypes (G) 1, 3, and 5 of the Japanese encephalitis virus (JEV) have been isolated in China, but the dominant genotype circulating in Chinese coastal areas remains unknown. We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis (JE) in the coastal provinces of China. Methods: In this study, we collected serum specimens from patients with JE in three coastal provinces of China (Guangdong, Zhejiang, and Shandong) from 2018 to 2020 and conducted JEV cross-neutralization tests against G1, G3, and G5. Results: Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong (92 patients), Zhejiang (192 patients), and Guangdong (77 patients), China, from 2018 to 2020. Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV. Two cases were confirmed to be infected with G1 JEV, 32 with G3 JEV, and two with G5 JEV. Conclusion: G3 was the primary infection genotype among JE cases with a definite infection genotype, and the infection caused by G5 JEV was confirmed serologically in China.
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Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Genótipo , Humanos , Encefalite Japonesa/epidemiologia , Encefalite Japonesa/virologia , China/epidemiologia , Vírus da Encefalite Japonesa (Espécie)/genética , Vírus da Encefalite Japonesa (Espécie)/isolamento & purificação , Vírus da Encefalite Japonesa (Espécie)/imunologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Criança , Pré-Escolar , Idoso , Anticorpos Antivirais/sangueRESUMO
Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.
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Encefalite Viral , Vírus , Humanos , Encefalite Viral/diagnóstico , Vírus/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase , DNA ViralRESUMO
Context: Squalene epoxidase (SQLE) is overexpressed in a variety of tumors, which may play an important role in their tumorigenesis, development, and prognosis. Aims: The aim of this study is to investigate the expression of SQLE and explore its clinicopathological significance in gastric cancer. Settings and Design: The correlation between its positive expression and the pathological characteristics of patients (such as sex, age, tumor size, survival, tumor differentiation, TNM staging, and lymph node metastasis) was analyzed. Materials and Methods: Immunohistochemical method was used to detect its expression in 107 cases of gastric carcinoma and 34 cases of tumor-adjacent tissues. Statistical Analysis Used: Counting data were analyzed by Chi-square test. Its overall survival was analyzed by Kaplan-Meier method and log-rank test. Its hazard factors were analyzed by Cox multivariate analysis. Results: The positive rate of SQLE in gastric cancer is 67.3%, which is higher than that in tumor-adjacent tissues (17.6%), <0.001. Expression of SQLE is closely related to tumor differentiation, TNM staging and lymph node metastasis (P = 0.030, P = 0.009, and P = 0.011, respectively). Furthermore, compared with those low expression of SQLE, the patients of overexpression had worse overall survival by Kaplan-Meier analysis (P = 0.025). Cox multivariate analysis shows that lymph node metastasis, tumor differentiation, SQLE, and TNM staging are independent factors for prognosis of gastric cancer (P = 0.003, 0.020, 0.018, and P = 0.001 respectively). Conclusions: SQLE is overexpressed in gastric cancer. It could be used for the diagnosis and prognosis of the gastric cancer patients.
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Esqualeno Mono-Oxigenase , Neoplasias Gástricas , Humanos , Relevância Clínica , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/genéticaRESUMO
OBJECTIVE: To study the effects of desmopressin (DDAVP) on coagulation factor â § (Fâ §) and activated partial thromboplastin time (APTT) in children with mild hemophilia A. METHODS: Eighteen children with mild hemophilia A were enrolled. DDAVP (0.3 µg/kgâ¢d) was injected intravenously for 5 days. Plasma Fâ § levels and APTT were measured before and after DDAVP treatment. RESULTS: In 16 of 18 children with mild hemophilia A, the bleeding symptoms, including the articular or musclar hematoma, were significantly alleviated as a result of DDAVP treatment. The plasma Fâ § levels increased significantly to (27±4)% and APTT was shortened to (66±10)s 60 minutes after the first dose of DDAVP treatment. The plasma Fâ § remained at the levels of 25%-30% during 3-4 days of DDAVP treatment. Five days after DDAVP treatment, the plasma Fâ § levels decreased [(21±3)%], and APTT was prolonged when compared with 1-4 days of DDAVP treatment. CONCLUSIONS: DDAVP treatment can increase plasma Fâ § levels and shorten APTT in children with mild hemophilia A. DDAVP is effective in the treatment of mild hemophilia A. The duration of DDAVP therapy for mild hemophilia A is recommended as 3 to 4 days.
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Desamino Arginina Vasopressina/uso terapêutico , Hemofilia A/tratamento farmacológico , Criança , Pré-Escolar , Fator VIII/análise , Hemofilia A/sangue , Humanos , Lactente , Masculino , Tempo de Tromboplastina ParcialRESUMO
The present study aimed to investigate the role and underlying mechanisms of long non-coding RNA (lncRNA) muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in the progression of Prostate cancer (PCa). MBNL1-AS1 and microRNA (miR)-181a-5p expression in PCa tissues and several human PCa cell lines were analyzed, respectively, using StarBasev3.0 project and RT-qPCR assay. After MBNL1-AS1 overexpression, cell proliferation, invasion and migration were, respectively, evaluated using CCK-8, colony formation, transwell and wound healing assays. Dual luciferase assay were used for analysis of the interactions among MBNL1-AS1, miR-181a-5p, and phosphatase and tensin homolog (PTEN). Subsequently, the expression of PTEN and proteins in PI3K/AKT/mTOR signaling was examined using western blot analysis after transfection with miR-181a-5p mimic. The rescue assays were performed to investigate the effects of MBNL1-AS1 and miR-181a-5p on the functions of PCa cells and the expression of PTEN/PI3K/AKT/mTOR signaling by co-transfection with MBNL1-AS1 plasmid and miR-181a-5p mimic. Results indicated that MBNL1-AS1 was conspicuously downregulated while miR-181a-5p upregulating in PCa tissues and cell lines. MBNL1-AS1 overexpression decreased the abilities of cell proliferation, invasion, and migration. Further study revealed that MBNL1-AS1 acted as a sponge for miR-181a-5p and positively regulated PTEN by a sponge effect. Additionally, rescue assays proved that the effect of MBNL1-AS1-upregulation on the proliferation, invasion, and migration of PCa cells was dependent on miR-181a-5p. Furthermore, miR-181a-5p overexpression counteracted the expression of PTEN and proteins in PI3K/AKT/mTOR signaling exerted by MBNL1-AS1-upregulation in PCa cells. This study suggests that MBNL1-AS1 inhibits the progression of PCa via sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR pathway.
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Proliferação de Células/genética , MicroRNAs/genética , Neoplasias da Próstata , RNA Antissenso , Transdução de Sinais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Humanos , Masculino , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Antissenso/genética , RNA Antissenso/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
PURPOSE: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% (P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (P = .316) and 5y DFS rates were 22. 6% and 23.2% (P = .928), respectively. CONCLUSION: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Vinorelbina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , China , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Gefitinibe/efeitos adversos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Tempo , Vinorelbina/efeitos adversosRESUMO
The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.
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Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Receptores ErbB/genética , Gefitinibe/uso terapêutico , Genômica , Humanos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Progesterone and adipoQ receptor family member 3 (PAQR3) and vascular endothelial growth factor (VEGF)-A are associated with tumorigenesis and progression. The aim of this study is to investigate the expression of PAQR3 and VEGF-A in pulmonary adenocarcinoma (PA) and explore their clinical and pathologic significance. The expressions of PAQR3 and VEGF-A protein were detected in 86 cases of human PA and 26 cases of tumor-adjacent tissue by immunohistochemistry. The positive rate of PAQR3 was 39.5% in PA, which was lower than that in tumor-adjacent tissues (80.8%), P=0.001. Negative expression of PAQR3 was obviously linked to tumor TNM stage, differentiation, and lymphatic metastasis; and P values were 0.013, 0.025, and 0.034, respectively. The positive expression rate of VEGF-A was 68.6% in human PA whichwas higher than that of tumor-adjacent tissues (11.5%), P<0.001. The positive expression of VEGF-A was correlated with tumor TNM stage, differentiation, and lymphatic metastasis, and P values were 0.026, 0.001 and P=0.001, respectively. The expression of PAQR3 was negatively correlated with the expression of VEGF-A (r=-0.698, P<0.001). Log-rank test statistical analysis suggested that patients with negative expression of PAQR3 or positive expression of VEGF-A had shorter overall survival. Cox multivariate analysis indicated that tumor TNM stage, differentiation, and lymphatic metastasis, and PAQR3 and VEGF-A expression were independent factors for prognosis of PA, and P values were 0.021, 0.017, 0.006, 0.018 and P=0.007 respectively. In conclusion, negative expression of PAQR3 and positive expression of VEGF-A are markedly correlated with tumor TNM classification, histologic grade, and lymphatic metastasis. Tumor TNM stage, differentiation, and lymphatic metastasis, negative expression of PAQR3, and positive expression of VEGF-A are risk factors for prognosis of patients with PA. Detection of PAQR3 and VEGF-A may be helpful to evaluate prognosis and infiltrative capability of PA.
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Radioresistance is an important factor affecting the radiotherapy effect of colorectal cancer (CRC). Allicin is a versatile sulfur-containing organic compound extracted from garlic (Allium sativum L.), which has many pharmacological effects. However, the effect of allicin on the sensitivity of CRC radiotherapy has not been confirmed. The present study is to observe the radiosensitivity effects of allicin and to explore its mechanism in CRC radiotherapy. The proliferation inhibition effects of allicin combined with X-ray radiotherapy in HCT116 cells were measured by growth curve of cell and colony formation assays. The cell apoptosis was detected by Hoechst 33258 nucleus staining assay. The migration ability of cells was detected by Transwell chamber migration assay. The animal model of CRC was established in BALB/c mice via transplantation of CT26 cell, and the radiosensitization effect of allicin on CRC was detected in vivo. The mRNA expressions of NF-κB, IKKß, and IκBα were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of NF-κB, p-NF-κB, IKKß, p-IKKß, IκBα, and p-IκBα were detected by western blotting. Our results showed that allicin improves the sensitivity of X-ray radiotherapy in CRC, and its mechanism may be associated with inhibition of NF-κB signaling pathway. These findings suggest that allicin may be used as a potential sensitizer for tumor radiotherapy in the clinic.
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Neoplasias Colorretais/radioterapia , NF-kappa B/metabolismo , Ácidos Sulfínicos/administração & dosagem , Animais , Apoptose/efeitos da radiação , Proliferação de Células/efeitos da radiação , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Dissulfetos , Células HCT116 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/genética , Tolerância a Radiação , Transdução de Sinais/efeitos da radiaçãoRESUMO
KN motif and ankyrin repeat domains 1 (Kank1) and ki67 are associated with tumorigenesis and progression. This paper researched the expression of Kank1 and Ki67 and their clinicopathologic significance in pulmonary adenocarcinoma (PA). We monitored the expression of KanK1 and ki67 in 94 cases of human PA and 31 cases of paracancerous tissue by the immunohistochemical method. The results showed that Kank1 protein was detected in 74.2% (41/94) of PA tissues, and they were associated with differentiation (P = 0.025) and lymphatic metastasis (P = 0.002). Kaplan-Meier analysis suggested that patients with low Kank1 expression had shorter overall survival in PA (P = 0.020). Ki67 protein was detected in 79.8% (75/94) of PA tissues, and they were associated with differentiation (P < 0.001), TNM classification (P = 0.007), and lymphatic metastasis (P = 0.044). Furthermore, Kaplan-Meier analysis showed that patients with overexpression of Ki67 had shorter overall survival (P = 0.014). Cox multivariate analysis showed that tumor differentiation, TNM classification, lymphatic metastasis, Kank1, and ki67 expression were independent factors for prognosis of PA (P = 0.012, 0.016, 0.007, 0.021 and P = 0.003 respectively). In conclusion, compared with paracancerous tissues, Kank1 had low expression, while Ki67 was overexpressed in PA. They are closely related to its occurrence and development, and the prognosis of patients with low expression of Kank1 or overexpression of ki67 was poor in PA. Kank1 and Ki67 can be helpful for diagnosing and detecting the prognosis of patients with PA.
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OBJECTIVES: Health-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group. MATERIALS AND METHODS: In the phase III ADJUVANT trial, patients with completely resected, stage II-IIIA (N1-N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups. RESULTS: At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75-63509.05, pâ¯=⯠0.019; LCSS, 1.13, 1.04-1.22, pâ¯=⯠0.003; TOI, 88.39, 4.40-1775.05, pâ¯=⯠0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42-0.90, pâ¯=⯠0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43-0.93, pâ¯=⯠0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33-0.77, pâ¯=⯠0.001). CONCLUSION: Adjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II-IIIA (N1-N2), EGFR-mutant NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Receptores ErbB/genética , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Estadiamento de Neoplasias , Qualidade de Vida , Vinorelbina/uso terapêuticoRESUMO
The purpose of this article is to study whether the overexpression of urokinase-type plasminogen activator (uPA) can promote the proliferation and fibrinolytic activity of human umbilical vein endothelial cells (HUVECs). The recombinant adenovirus vectors containing the human uPA gene were constructed and transfected into HUVECs. In this study, the mRNA of uPA was detected by qPCR, and the uPA protein was measured by Western blot. The cell proliferation was measured using MTT. The fibrinolytic activity of uPA was quantified using a colorimetric assay. We also measured MMP2 (metalloproteinase-2), MMP9 (metalloproteinase-9), and VEGF (vascular endothelial growth factor) proteins using ELISA. The results showed that the levels of the uPA mRNA and the protein in the overexpression group were significantly higher compared to the other groups, (P < 0.05). The cell proliferation and uPA activity were increased significantly in the overexpression group, compared to the other groups, (P < 0.05). The secretions of MMP2, MMP9, and VEGF in the overexpression group were significantly higher than they were in the other two groups (P < 0.05). In conclusion, we successfully transfected a recombined adenovirus vector carrying uPA into a HUVEC. The exogenous uPA gene could transcribe and secrete the uPA protein in the HUVECs. The overexpression of uPA can increase cell proliferation and uPA activity. It can improve the invasion and angiogenesis ability in HUVECs by promoting their secretions of MMP2, MMP9, and VEGF.
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OBJECTIVE: In the era of fast track surgery, early and accurately estimating whether postoperative length of stay (p-LOS) will be prolonged after lung cancer surgery is very important, both for patient's discharge planning and hospital bed management. Pulmonary function tests (PFTs) are very valuable routine examinations which should not be underutilized before lung cancer surgery. Thus, this study aimed to establish an accurate but simple prediction tool, based on PFTs, for achieving a personalized prediction of prolonged p-LOS in patients following lung resection. METHODS: The medical information of 1257 patients undergoing lung cancer surgery were retrospectively reviewed and served as the training set. p-LOS exceeding the third quartile value was considered prolonged. Using logistic regression analyses, potential predictors of prolonged p-LOS were identified among various preoperative factors containing PFTs and intraoperative factors. A nomogram was constructed and subjected to internal and external validation. RESULTS: Five independent risk factors for prolonged p-LOS were identified, including older age, being male, and ratio of residual volume to total lung capacity (RV/TLC) ≥ 45.0% which is the only modifiable risk factor, more invasive surgical approach, and surgical type. The nomogram comprised of these five predictors exhibited sufficient predictive accuracy, with the area under the receiver operating characteristic curve (AUC) of 0.76 [95% confidence interval (CI) 0.73-0.79] in the internal validation. Also its predictive performance remained fine in the external validation, with the AUC of 0.70 (95% CI 0.60-0.79). The calibration curves showed satisfactory agreements between the model predicted probability and the actually observed probability. CONCLUSIONS: Preoperative amelioration of RV/TLC may prevent lung cancer patients from unnecessary prolonged p-LOS. The integrated nomogram we developed could provide personalized risk prediction of prolonged p-LOS. This prediction tool may help patients perceive expected hospital stays and enable clinicians to achieve better bed management after lung cancer surgery.
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Hepatic injury is one of the most common digestive system diseases worldwide in clinic. Guanylic acid or guanosine monophosphate (GMP) was an important component of nucleotides, which is mainly in the form of sodium salt (disodium guanylate, GMP-Na2 ). However, its effect on hepatic injury has not yet been investigated. This study is to investigate the protective effects of GMP-Na2 on acute hepatic injury induced by carbon tetrachloride (CCl4 ), and to explore its mechanism. The hepatic injury models of mice and HL-7702 cells were induced by CCl4 . The alanine transaminase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (T-AOC) were determined by biochemical method. Hematoxylin-eosin staining were used to determine the morphological changes on liver tissue in mice. The mRNA and protein expressions of caspase-3, Bax, and Bcl-2 were detected by RT-PCR and Western blot analysis. Our results show that GMP-Na2 treatment significantly decreased the activities of ALT and AST, and the levels of MDA as well as increased the levels of SOD, GSH-Px, and T-AOC. Importantly, GMP-Na2 effectively enhanced the antiapoptosis function by upregulating Bcl-2 expression and downregulating caspase-3 and Bax expressions in vivo and in vitro. Moreover, the histopathological changes of liver tissue were obviously improved after GMP-Na2 treatment. These findings suggest that GMP-Na2 has protective effects on hepatic injury, and its mechanisms may be associated with antioxidative stress and antiapoptosis.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Guanosina Monofosfato/farmacologia , Fígado/efeitos dos fármacos , Animais , Fígado/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacosRESUMO
INTRODUCTION: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized. METHODS: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted. RESULTS: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib. CONCLUSIONS: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored.
Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/secundário , Quimioterapia Adjuvante/efeitos adversos , Gefitinibe/efeitos adversos , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/epidemiologia , Análise Espaço-Temporal , Adolescente , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Taxa de Sobrevida , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: Human bocavirus (HBoV) is a parvovirus recently found to possibly cause respiratory tract disease in children and adults. This study investigated HBoV infection and its clinical characteristics in children younger than five years of age suffering from acute lower respiratory tract infection in Beijing Children's Hospital. METHODS: Nasopharyngeal aspirates were collected from children suffering from acute lower respiratory tract infection during the winters of 2004 to 2006 (from November through the following February). HBoV was detected by polymerase chain reaction amplification and virus isolation and the amplification products were sequenced for identification. RESULTS: HBoV infection was detected in 16 of 333 study subjects. Coinfections with respiratory syncytial virus were detected in 3 of 16 HBoV positive patients with acute lower respiratory tract infection. The median age for HBoV positive children was 8 months (mean age, 17 months; range, 3 to 57 months). Among the HBoV positive children, 14 were younger than 3 years old, 9 were younger than 1 year old and 7 were younger than 6 months. These 16 positive HBoV children exhibited coughing and abnormal chest radiography findings and more than 60% of these children had wheezing and fever. Ten children were clinically diagnosed with pneumonia, 2 bronchiolitis, 2 acute bronchitis and 2 asthma. One child died. CONCLUSIONS: HBoV was detected in about 5% of children with acute lower respiratory infection seen in Beijing Children's Hospital. Further investigations regarding clinical and epidemiologic characteristics of HBoV infection are needed.