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1.
J Transl Med ; 19(1): 342, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372882

RESUMO

BACKGROUND: We tried to elaborate the molecular mechanism of ETS-like transcription factor 4 (ELK4) affecting gastric cancer (GC) progression through M2 polarization of macrophages mediated by lysine-specific demethylase 5A (KDM5A)-Praja2 (PJA2)-kinase suppressor of ras 1 (KSR1) axis. METHODS: GC expression dataset was obtained from GEO database, and the downstream regulatory mechanism of ELK4 was predicted. Tumor-associated macrophages (TAMs) were isolated from GC tissues. The interaction among ELK4, KDM5A, PJA2 and KSR1 was analyzed by dual luciferase reporter gene, ChIP and Co-IP assays. The stability of KSR1 protein was detected by cycloheximide (CHX) treatment. After TAMs were co-cultured with HGC-27 cells, HGC-27 cell biological processes were assessed through gain- and loss-of function assays. Tumorigenicity was detected by tumorigenicity test in nude mice. RESULTS: In GC and TAMs, ELK4, KDM5A and KSR1 were highly expressed, while PJA2 was lowly expressed. M2 polarization of macrophages promoted the development of GC. ELK4 activated KDM5A by transcription and promoted macrophage M2 polarization. KDM5A inhibited the expression of PJA2 by removing H3K4me3 of PJA2 promoter, which promoted M2 polarization of macrophages. PJA2 reduced KSR1 by ubiquitination. ELK4 promoted the proliferative, migrative and invasive potentials of GC cells as well as the growth of GC xenografts by regulating KSR1. CONCLUSION: ELK4 may reduce the PJA2-dependent inhibition of KSR1 by transcriptional activation of KDM5A to promote M2 polarization of macrophages, thus promoting the development of GC.


Assuntos
Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Humanos , Ativação de Macrófagos , Macrófagos , Camundongos , Camundongos Nus , Proteína 2 de Ligação ao Retinoblastoma , Neoplasias Gástricas/genética , Ativação Transcricional , Ubiquitina-Proteína Ligases , Proteínas Elk-4 do Domínio ets
2.
Pathol Oncol Res ; 27: 581542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34385891

RESUMO

Gastric cancer (GC) is one of the major malignancies worldwide. Emerging evidence has revealed the potential involvement of long noncoding RNA (lncRNA) in human genetic disorders and cancer, but the role of LOC100505817 remains unknown. Thus, in this study, we isolated tissues from GC patients to characterize the functional importance of LOC100505817 in GC tumorigenesis. We also proposed a hypothesis that the regulation of Wnt/ß-catenin pathway by LOC100505817 was regulated by miR-20a-mediated WT1. After the collection of cancer tissues and adjacent tissues were obtained from GC patients, expression of LOC100505817, Wnt/ß-catenin pathway- and EMT-related genes was quantified. Ectopic expression and knockdown experiments were applied in order to investigate the protective role of LOC100505817 in the progression of GC. Subsequently, cell viability, flow cytometry for apoptosis and cell cycle were detected via CCK-8, while migration and invasion were determined using scratch test and Transwell assay respectively. Then interactions among LOC100505817, miR-20a and WT1 were explored by dual luciferase reporter gene assay, RNA pull down assay and RNA binding protein immunoprecipitation (RIP) assay. The results found poor expression LOC100505817 was poorly expressed in GC cells and tissues. Overexpressed LOC100505817 resulted in the significant reduction of cell proliferation, migration and invasion as well as the expression of Wnt2b, ß-catenin, CyclinD1, N-cadherin, Vimentin and snail, while increased cell apoptosis along with the expression of E-cadherin. Wnt/ß-catenin pathway and EMT in GC cells were suppressed by LOC100505817 through miR-20a-inhibted WT1. In summary, our results provided evidence suggesting that LOC100505817 inhibits GC through LOC100505817-mediated inhibition of Wnt/ß-catenin pathway, that leads to the overall restraining of GC cell proliferation, migration and invasion through miR-20a-reduced WT1.

3.
J Interv Cardiol ; 2021: 9915759, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220369

RESUMO

Background: Treatment of coronary intermediate lesions remains a controversy, and the role of arterial remodeling patterns determined by intravascular ultrasound in intermediate lesion is still not well known. The aim of this study was to investigate the impact of arterial remodeling of intermediate coronary lesions on long-term clinical outcomes. Methods: Arterial remodeling patterns were assessed in 212 deferred intermediate lesions from 162 patients after IVUS examination. Negative, intermediate, and positive remodeling was defined as a remodeling index of <0.88, 0.88∼1.0, and >1.0, respectively. The primary endpoint was the composite vessel-oriented clinical events, defined as the composition of target vessel-related cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. Quantitative flow ratio was assessed for evaluating the functional significance of intermediate lesions. Results: 72 intermediate remodeling lesions were present in 66 patients, whereas 77 negative remodeling lesions were present in 71 patients, and 63 positive remodeling lesions were present in 55 patients. Negative remodeling lesions had the smallest minimum lumen area (4.16 ± 1.03 mm2 vs. 5.05 ± 1.39 mm2 vs. 4.85 ± 1.76 mm2; P < 0.01), smallest plaque burden (63.45 ± 6.13% vs. 66.12 ± 6.82% vs. 71.17 ± 6.45%; P < 0.01), and highest area stenosis rate (59.32% ± 10.15% vs. 54.61% ± 9.09% vs. 51.67% ± 12.96%; P < 0.01). No significant difference was found in terms of quantitative flow ratio among three groups. At 5 years follow-up, negative remodeling lesions had a higher rate of composite vessel-oriented clinical event (14.3%), compared to intermediate (1.4%, P=0.004) or positive remodeling lesions (4.8%, P=0.06). After adjusting for multiple covariates, negative remodeling remained an independent determinant for vessel-oriented clinical event (HR: 4.849, 95% CI 1.542-15.251, P=0.007). Conclusion: IVUS-derived negative remodeling is associated with adverse long-term clinical outcome in stable patients with intermediate coronary artery stenosis.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/diagnóstico por imagem , Infarto do Miocárdio/epidemiologia , Revascularização Miocárdica/estatística & dados numéricos , Ultrassonografia de Intervenção , Remodelação Vascular , Idoso , Velocidade do Fluxo Sanguíneo , Doença da Artéria Coronariana/terapia , Estenose Coronária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Estudos Retrospectivos
4.
Int J Cardiovasc Imaging ; 37(10): 2803-2813, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34059977

RESUMO

Discrepancy between coronary lesion severity and functional significance has always been a relevant issue in the management of patients undergoing coronary angiography and/or revascularization. We sought to investigate the relationship between quantitative flow ratio (QFR)-derived microcirculatory indices and anatomical-functional mismatch/reverse mismatch in intermediate coronary lesions. Intravascular ultrasound (IVUS) imaging and QFR were analyzed in 117 de novo intermediate coronary lesions. Lesions with QFR ≤ 0.8 were considered hemodynamically significant. Anatomical significance of the lesions was defined according to the best cutoff value of combined IVUS parameters for predicting QFR ≤ 0.8. QFR-derived microcirculatory indices including contrast-flow QFR minus fixed-flow QFR (cQFR-fQFR), hyperemic flow velocity and angiography-derived index of microcirculatory resistance (IMRangio) were calculated. The best cutoff values of IVUS parameters for predicting QFR ≤ 0.8 were minimum lumen area (MLA) 3.1mm2 and plaque burden (PB) 70%, with area under the curve of 0.635 and 0.703, respectively. The total discordance rate of lesion functional significance between IVUS and QFR assessments was 26.5%, with 21 lesions (17.9%) being classified as mismatch (MLA ≤ 3.1mm2 and PB ≥ 70% and QFR > 0.8) and 10 lesions (8.5%) as reverse-mismatch (MLA > 3.1 mm2 or PB < 70% and QFR ≤ 0.8). At multivariate analysis, IMRangio was identified as an independent predictor of mismatch (OR1.675, 95%CI:1.176-2.386, P = 0.004), whereas hyperemic flow velocity was identified as an independent predictor of reverse-mismatch (OR 1.233, 95%CI:1.073-1.416, P = 0.003). In intermediate coronary lesions, although MLA 3.1mm2 and PB 70% determined by IVUS are predictive of QFR-defined functional significance, the discordance rate remains substantial. QFR-derived microcirculatory indices are independently associated with anatomical-functional discordance between IVUS and QFR assessments.

5.
J Transl Med ; 19(1): 37, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472665

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common type of lung cancer. Extracellular vehicles (EVs) are nano-sized particles containing proteins, lipids, and miRNAs secreted by various cells, which play important roles in the development of lung cancer by regulating a wide range of signaling pathways. This study focused on elucidating a potential mechanism by which EVs promote the development of NSCLC. METHODS: Expression levels of miR-744, SUV39H1, Smad9, and BMP4 in clinical tissue samples of NSCLC patients and cell lines were quantified by RT-qPCR and/or western blot analysis. The interaction between SUV39H1 and miR-744 was identified by dual-luciferase reporter assay. miR-744, SUV39H1, and BMP4 expression levels were modulated in A549 and H460 cells, in order to evaluate their effects on cell proliferation, colony formation and cell cycle. A NSCLC xenograft mouse model was used to verify the in vitro findings. NSCLC cell-derived EVs and normal bronchial epithelial cell-derived EVs were isolated and their roles in NSCLC development were evaluated in vivo and in vitro. RESULTS: miR-744 expression was lower in cancer cell-derived derived EVs than in normal lung epithelial cell-derived EVs. Reduced miR-744 expression in EVs upregulated SUV39H1 in NSCLC cells and further increased BMP4 levels to promote NSCLC development. BMP4 was upregulated in NSCLC cells upon suppression of Smad9 mediated by SUV39H1. Reduced miR-744 expression transferred from cancer cell-derived EVs into NSCLC cells enhanced cancer development. CONCLUSION: Overall, our findings unveiled a mechanism whereby miR-744 delivered by NSCLC-derived EVs upregulated SUV39H1, activating the Smad9/BMP9 axis and thus promoted cancer development.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroRNAs , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Vesículas Extracelulares/metabolismo , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Metiltransferases , Camundongos , MicroRNAs/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteína Smad8
6.
Am J Physiol Gastrointest Liver Physiol ; 320(5): G816-G828, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33236952

RESUMO

Upregulating the expression of long noncoding RNA LINC00982 controlled cell proliferation in gastric cancer, but the regulatory molecular mechanisms are yet to be expounded. We here aimed to elaborate how LINC00982 regulated the malignancy of gastric cancer cells. RT-qPCR and Western blot analysis were used to detect the expression of LINC00982 and cathepsin F (CTSF) in gastric cancer tissues and cells. Modulatory effect of LINC00982 on gastric cancer cells was assessed by CCK-8, colony formation, Transwell migration, and invasion assays. The relationship between LINC00982, YRPW motif 1 (HEY1), and CTSF was examined by RNA-binding protein immunoprecipitation, luciferase assay, and chromatin immunoprecipitation, and their interaction in the regulation of gastric cancer cellular functions was analyzed by performing gain-of-function and rescue assays. The nude mouse model of tumor formation was developed to examine the effects of LINC00982 on tumorigenesis. LINC00982 was lowly expressed in gastric cancer tissues, whereas its overexpression impaired the proliferative, migratory, and invasive properties of gastric cancer cells. Furthermore, LINC00982 could bind to transcription factor HEY1 and inhibited its expression. Through blocking the binding of HEY1 to CTSF promoter, LINC00982 promoted the expression of CTSF. Overexpression of HEY1 or inhibition of CTSF could reverse the antitumor effects of LINC00982 on gastric cancer, which were further demonstrated in vivo. All these taken together, LINC00982 acted as a tumor suppressor in gastric cancer, which is therefore suggested to be a potential antitumor target for gastric cancer.NEW & NOTEWORTHY We identified LINC00982 as a promising antitumor target for the treatment of patients with gastric cancer. We also determined a regulatory network involved in the pathophysiology of gastric cancer wherein LINC00982 could bind to HEY1 to impair its binding to cathepsin F (CTSF) promoter and hence promote CTSF expression, which aids in better understanding of molecular mechanisms related to gastric tumorigenesis.

7.
Cancer Gene Ther ; 28(3-4): 250-264, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33299140

RESUMO

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating research has highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the clinical significance of serum-derived exosomal miR-let-7e as a biomarker in the metastasis of NSCLC. Initially, the expression of miR-let-7e, SUV39H2, and CDH1 in human NSCLC tissues and exosomes isolated from the serum of NSCLC patients was determined by RT-qPCR, demonstrating that miR-let-7e was downregulated in NSCLC tissues and serum-derived exosomes, while SUV39H2 was upregulated in NSCLC tissues. Kaplan-Meier method revealed that both lower miR-let-7e expression and higher SUV39H2 expression were correlated with a lower survival rate of NSCLC patients. Next, SUV39H2 was predicted and validated to be a target of miR-let-7e using dual-luciferase reporter assay. NSCLC H1299 cells following ectopic expression and depletion experiments of miR-let-7e and SUV39H2 were treated with serum-derived exosomes, after which the viability, migration, and invasion of H1299 cells were detected using CCK-8 and Transwell assays. Further, in vivo experiments were conducted to elucidate the effect of exosomal miR-let-7e on tumorigenesis. Results revealed that miR-let-7e overexpression in serum-derived exosomes inhibited SUV39H2, resulting in impaired cell viability, migration, and invasion in vitro as well as delayed tumor growth in vivo. In conclusion, the key findings of the current study demonstrate that exosomal miR-let-7e from serum possesses anticarcinogenic properties against NSCLC via the SUV39H2/LSD1/CDH1 axis.

8.
Front Med (Lausanne) ; 7: 456, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195288

RESUMO

Aptamers are special types of single-stranded DNA generated by a process called systematic evolution of ligands by exponential enrichment (SELEX). Due to significant advances in the chemical synthesis and biotechnological production, aptamers have gained considerable attention as versatile building blocks for the next generation of soft materials. Hydrogels are high water-retainable materials with a three-dimensional (3D) polymeric network. Aptamers, as a vital element, have greatly expanded the applications of hydrogels. Due to their biocompatibility, selective binding, and molecular recognition, aptamer-based hydrogels can be utilized for bioanalytical and biomedical applications. In this review, we focus on the latest strategies of aptamer-based hydrogels in bioanalytical and biomedical applications. We begin this review with an overview of the underlying design principles for the construction of aptamer-based hydrogels. Next, we will discuss some bioanalytical and biomedical applications of aptamer-based hydrogel including biosensing, target capture and release, logic devices, gene and cancer therapy. Finally, the recent progress of aptamer-based hydrogels is discussed, along with challenges and future perspectives.

9.
World J Clin Cases ; 8(20): 4917-4921, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33195661

RESUMO

BACKGROUND: Woven coronary artery is an extremely rare disease with unknown etiology. This condition is difficult to diagnosis by traditional methods. CASE SUMMARY: A 67-year-old male presented to the cardiology department with a history of mild chest pain for 6 mo. Coronary computed-tomography angiography revealed a soft plaque with a 40% stenosis in the right coronary artery (RCA). A linear shadow was seen both on left circumflex (LCX) and RCA. Further coronary angiography showed an 80% regional stenosis in the area proximal of LCX and RCA, and it was divided into different channels with diffuse stenosis. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) were performed in RCA. These confirmed a woven coronary artery. No stent was implanted. He remained asymptomatic during the 5-year follow-up period. CONCLUSION: Woven coronary artery can be distinguished from spontaneous dissection and revascularization of thrombosis. IVUS and OCT are useful in obtaining a definite diagnosis, which decreases chances of unnecessary intervention.

10.
Exp Ther Med ; 20(6): 141, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33093879

RESUMO

The present study aimed to investigate the expression and predictive value of serum hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in patients with burns following treatment. A total of 84 patients with burns treated in Jinan City People's Hospital (Jinan, China) between June 2015 and August 2017 were selected and their clinical information was collected. The expression levels of HIF-1α and VEGF before and after treatment were detected via ELISA, and HIF-1α and VEGF levels in patients with effective and ineffective treatment were compared. The predictive values of HIF-1α and VEGF in clinical efficacy were determined using receiver operating characteristic (ROC) curves, and independent risk factors affecting treatment inefficacy were analyzed via multivariate logistic regression. It was revealed that HIF-1α decreased significantly (P<0.05) while VEGF significantly increased in patients after treatment. Patients with effective treatment presented significantly lower HIF-1α levels and higher VEGF levels compared with those with ineffective treatment. The ROC curve indicated that the area under the curve (AUC) of HIF-1α for treatment efficacy was 0.795, the 95% CI was 0.666-0.924, the specificity and sensitivity were 68.75 and 80.88%, respectively, and the Youden index was 49.63%. For VEGF, the AUC, 95% CI, specificity, sensitivity and Youden index were 0.826, 0.725-0.928, 68.75, 82.35 and 51.10% respectively. Moreover, under the joint detection of HIF-1α and VEGF, the AUC was 0.847, 95% CI was 0.746-0.947, specificity and sensitivity were 87.50 and 66.18%, respectively, with a Youden index of 53.68%. Multivariate analysis demonstrated that higher HIF-1α level, lower VEGF level and higher burn degree before treatment were independent risk factors for treatment inefficacy. HIF-1α levels decreased and VEGF levels increased in burn patients after treatment. HIF-1α and VEGF before treatment may therefore serve as predictors for treatment efficacy.

11.
Sensors (Basel) ; 20(18)2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32906707

RESUMO

The vehicular Internet of Things (IoT) comprises enabling technologies for a large number of important applications including collaborative autonomous driving and advanced transportation systems. Due to the mobility of vehicles, strict application requirements, and limited communication resources, the conventional centralized control fails to provide sufficient quality of service for connected vehicles, so a decentralized approach is required in the vicinity to satisfy the requirements of delay-sensitive and mission-critical applications. A decentralized system is also more resistant to the single point of failure problem and malicious attacks. Blockchain technology has been attracting great interest due to its capability of achieving a decentralized, transparent, and tamper-resistant system. There are many studies focusing on the use of blockchain in managing data and transactions in vehicular environments. However, the application of blockchain in vehicular environments also faces some technical challenges. In this paper, we first explain the fundamentals of blockchain and vehicular IoT. Then, we conduct a literature review on the existing research efforts of the blockchain for vehicular IoT by discussing the research problems and technical issues. After that, we point out some future research issues considering the characteristics of both blockchain and vehicular IoT.

12.
Oncol Lett ; 19(4): 3035, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256806

RESUMO

[This corrects the article DOI: 10.3892/ol.2019.11011.].

13.
Catheter Cardiovasc Interv ; 95 Suppl 1: 598-605, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31957972

RESUMO

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor has become the standard of care to reduce thrombotic events in patients with acute coronary syndrome or after percutaneous coronary intervention (PCI). The role of routine platelet function testing (PFT) in patients treated with DAPT after PCI remains controversial and evidence of PFT-guided antiplatelet therapy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI is limited. METHODS: We analyzed 1,353 consecutive STEMI patients undergoing primary PCI. PFT was performed 72 hr postprocedure using a vasodilator-stimulated phosphoprotein assay. The primary endpoint of major adverse cardio-cerebral events (MACCEs) was defined as a composite of all-cause death, cardiac death, nonfatal myocardial infarction, target vessel revascularization, and ischemic stroke. Patients with high platelet reactivity (HPR) were randomized to receive an intensified antiplatelet strategy by switching from clopidogrel to ticagrelor (HPR switch group) or to continue on clopidogrel (HPR nonswitch group). One-year clinical outcomes were compared among the groups. RESULTS: The baseline clinical characteristics were comparable across all groups (all p > .05). At the 1-year clinical follow-up, the primary endpoint of MACCE was significantly higher in the HPR nonswitch group than in the non-HPR and HPR switch groups (19.49% vs. 10.20% or 8.57%, p < .05), which was mainly caused by higher mortality (14.87% vs. 4.51% or 5.71%, p < .05). Major bleeding events were comparable across the groups. CONCLUSIONS: In STEMI patients with HPR, identified by vasodilator stimulated phosphoprotein (VASP)-determined PFT, switching clopidogrel to ticagrelor could significantly improve 1-year clinical outcomes without increasing the risk of bleeding.


Assuntos
Plaquetas/efeitos dos fármacos , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Testes de Função Plaquetária , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Aspirina/administração & dosagem , Biomarcadores/sangue , Plaquetas/metabolismo , Moléculas de Adesão Celular/sangue , China , Clopidogrel/administração & dosagem , Substituição de Medicamentos , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/mortalidade , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Proteínas dos Microfilamentos/sangue , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Fosfoproteínas/sangue , Inibidores da Agregação Plaquetária/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Ticagrelor/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
14.
Oncol Lett ; 18(6): 6885-6890, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788128

RESUMO

Peripheral primitive neuroectodermal tumors (pPNETs) are rare, small cell carcinomas with a poor prognosis. The aim of the present study was to describe therapeutic approaches, outcomes and probable prognostic factors. The clinical features, treatments, and outcomes of 89 consecutive patients with pPNET treated at the Peking Union Medical College Hospital from 1999 to 2018 were retrospectively reviewed. A total of 43 males and 46 females were included in the study, with a median age of 25 years (range, 5-73 years). The predominantly affected regions were the abdomen and pelvis, followed by the thoracopulmonary region. The mean primary tumor size was 12.6 cm (range, 1-30 cm). A total of 16 patients (18%) initially presented with metastasis. A total of 46 patients received combined therapy, 35 received mono-therapy, and 8 underwent only biopsy with no further treatment. The period of observation ranged from 1-232 months. The median overall survival (OS) time was 15 months [95% confidence interval (CI), 9-21 months], with 3- and 5-year OS rates of 32 and 25%, respectively. Large tumor size [adjusted hazard ratio (aHR)=3.65; 95% CI, 2.07-6.42; P<0.001), metastasis at initial presentation (aHR=4.34, 95% CI, 2.23-8.42; P<0.001), and combined modality treatment (aHR=0.16, 95% CI, 0.06-0.39; P<0.001) were significantly associated with OS. The prognosis of pPNET is, overall, poor. Large tumor size and metastasis at initial presentation are associated with poorer outcomes. This highly malignant tumor requires an aggressive combination of radical resection, chemotherapy and radiotherapy, when indicated.

15.
Head Neck ; 41(12): 4151-4163, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31566825

RESUMO

BACKGROUND: The purpose of this study was to investigate significance of HPV16 DNA/p16 for survival of patients with laryngeal squamous cell carcinoma (LSCC). METHODS: HPV16 DNA and p16 status in 812 LSCC patients were determined. The survival was performed using Kaplan-Meier estimates and Cox model. RESULTS: Compared with HPV negativity, adjusted HRs for HPV16 positivity were 0.57, 95% CI, 0.38 to 0.87; 0.60, 0.40 to 0.88; and 0.65, 0.46 to 0.94 for disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS), respectively. Additionally, for p16 expression, aHRs were 0.68, 95% CI, 0.48 to 0.96; 0.72, 0.52 to 0.98; and 0.73, 0.54 to 0.99 for DSS, RFS, and OS, respectively. Finally, for combined analysis, patients with both HPV16-positivity/p16-positivity had much better prognosis than those with either negativity. Such above survivals are more significantly better in never smokers. CONCLUSION: Our findings suggest that HPV16/p16 may affect survival outcomes of LSCC patients, particularly in never smokers.


Assuntos
Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Viral/genética , Papillomavirus Humano 16/genética , Neoplasias Laríngeas/virologia , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Taxa de Sobrevida
16.
Mol Ther Nucleic Acids ; 18: 166-182, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31557618

RESUMO

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular progress in lung adenocarcinoma. In this study, to identify cancer-related lncRNAs and genes, we screened for those lncRNAs that were differentially expressed in lung adenocarcinoma, which revealed LINC00628 overexpression and low expression of laminin subunit alpha 3 (LAMA3). This was further validated in the cancerous tissues from patients diagnosed with lung adenocarcinoma. Thereafter, we explored the functional relevance of LINC00628 and LAMA3 in lung adenocarcinoma by analyzing the recruitment of DNA methyltransferase (DNMT) and the cellular processes of lung adenocarcinoma cells following treatments that induced LINC00628 overexpression or LINC00628 silencing or with 5-azacytidine (5-Aza, a DNMT inhibitor). The results showed that LINC00628 silencing decreased cell proliferation, migration, and invasion as well as the drug resistance of lung adenocarcinoma cells to vincristine (VCR). The results were opposite in the cells with LAMA3 demethylation induced by 5-Aza treatment. Further research indicated that LINC00628 recruited DNMT1, DNMT3A, and DNMT3B to promote the methylation of LAMA3 promoter, thereby decreasing its expression. Moreover, an in vivo experiment was performed in nude mice to assess the tumor growth ability and drug resistance of human lung adenocarcinoma cells. It was observed that LINC00628 silencing or 5-Aza treatment inhibited the in vivo tumor growth ability of the human lung adenocarcinoma cells and reduced their resistance to VCR. Altogether, our results provide evidence of a mechanism by which LINC00628 silencing exerts an inhibitory role in lung adenocarcinoma by modulating the DNA methylation of LAMA3, indicative of a novel molecular target for treatment of lung adenocarcinoma patients showing resistance to VCR.

17.
J Cell Mol Med ; 23(9): 6411-6428, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31317666

RESUMO

Lung adenocarcinoma is a common histologic type of lung cancer with a high death rate globally. Increasing evidence shows that long non-coding RNA H19 (lncRNA H19) and CDH1 methylation are involved in multiple tumours. Here, we tried to investigate whether lncRNA H19 or CDH1 methylation could affect the development of lung adenocarcinoma. First, lung adenocarcinoma tissues were collected to detect CDH1 methylation. Then, the regulatory mechanisms of lncRNA H19 were detected mainly in concert with the treatment of overexpression of lncRNA H19, siRNA against lncRNA H19, overexpression of CDH1 and demethylating agent A-5az in lung adenocarcinoma A549 cell. The expression of lncRNA H19 and epithelial-mesenchymal transition (EMT)-related factors as well as cell proliferation, sphere-forming ability, apoptosis, migration and invasion were detected. Finally, we observed xenograft tumour in nude mice so as to ascertain tumorigenicity of lung adenocarcinoma cells. LncRNA H19 and methylation of CDH1 were highly expressed in lung adenocarcinoma tissues. A549 cells with silencing of lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation by demethylating agent 5-Az had suppressed cell proliferation, sphere-forming ability, apoptosis, migration and invasion, in addition to inhibited EMT process. Silencing lncRNA H19 could reduce methylation level of CDH1. In vivo, A549 cells with silencing lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation exhibited low tumorigenicity, reflected by the smaller tumour size and lighter tumour weight. Taken together, this study demonstrates that silencing of lncRNA H19 inhibits EMT and proliferation while promoting apoptosis of lung adenocarcinoma cells by inhibiting methylation of CDH1 promoter.


Assuntos
Adenocarcinoma de Pulmão/genética , Antígenos CD/genética , Caderinas/genética , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas/genética , RNA Longo não Codificante/genética , Células A549 , Adulto , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Metilação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Adulto Jovem
18.
Am J Physiol Lung Cell Mol Physiol ; 316(5): L918-L933, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30628487

RESUMO

The involvement of several microRNAs (miRs) in the initiation and development of tumors through the suppression of the target gene expression has been highlighted. The aberrant expression of miR-181d-5p and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was then screened by microarray analysis. In the present study, we performed a series of in vivo and in vitro experiments for the purpose of investigating their roles in NSCLC and the underlying mechanism. There was a high expression of CDKN3, whereas miR-181d-5p was downregulated in NSCLC. Quantitative RT-PCR, Western blot analysis, and dual-luciferase reporter gene assay further identified that CDKN3 could be negatively regulated by miR-181d-5p. Moreover, the upregulation of miR-181d-5p or silencing of CDKN3 could inactivate the Akt signaling pathway. A549 with the lowest miR-181d-5p and H1975 with the highest CDKN3 among the five NSCLC cell lines (H1299, A549, H1975, NCI-H157, and GLC-82) were adopted for in vitro experiments, in which expression of miR-181d-5p and CDKN3 was altered by transfection of miR-181d-5p mimic/inhibitor or siRNA-targeting CDKN3. Afterwards, cell proliferation, apoptosis, invasion, migration, and angiogenesis, as well as epithelial-mesenchymal transition (EMT), were evaluated, and tumorigenicity was assessed. In addition, an elevation in miR-181d-5p or depletion in CDKN3 led to significant reductions in proliferation, invasion, migration, angiogenesis, EMT, and tumorigenicity of NSCLC cells, coupling with increased cell apoptosis. In conclusion, this study highlights the tumor-suppressive effects of miR-181d-5p on NSCLC via Akt signaling pathway inactivation by suppressing CDKN3, thus providing a promising therapeutic strategy for the treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas Inibidoras de Quinase Dependente de Ciclina/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Proteínas Inibidoras de Quinase Dependente de Ciclina/antagonistas & inibidores , Proteínas Inibidoras de Quinase Dependente de Ciclina/genética , Fosfatases de Especificidade Dupla/antagonistas & inibidores , Fosfatases de Especificidade Dupla/genética , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Xenoenxertos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais
19.
Ann Transl Med ; 7(23): 759, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32042775

RESUMO

Background: The purpose of this study was to investigate the association between HPV 16 status and survival outcomes in patients with non-oropharyngeal squamous carcinoma (non-OPSCC). Methods: Patients with non-OPSCC diagnosed between 2006 and 2016 were included in this study. The presence of HPV 16 DNA was confirmed by quantitative real-time polymerase chain reaction. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching (PSM). Results: Overall, 1,539 patients with adequate specimens were identified, of whom 131 (8.51%) were positive for HPV 16. Compared to HPV 16-negative patients, the adjusted hazard ratios (aHR) for HPV 16-positive non-OPSCC patients were 0.77 and 0.81 for disease-specific survival (DSS) and overall survival (OS), respectively. Additionally, the larynx was the only subsite in which DSS was significantly improved. After PSM, cohorts consisted of 129 patients in the HPV 16-positive group and 129 in the HPV 16-negative group. HPV 16-positive non-OPSCC patients had favorable survival outcomes, however, these outcomes were not significantly different compared to HPV 16-negative patients. Stratified analysis performed according to primary site showed that only in the larynx was HPV 16-positive status a significant factor for predicting favorable DSS. Conclusions: Our findings indicate that HPV 16-positive non-OPSCC patients did not have significantly better survival outcomes compared to HPV 16-negative patients.

20.
Pathol Oncol Res ; 25(1): 369-376, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29134462

RESUMO

This study aims to explore the roles of fibroblast activation protein (FAP) and hepatocyte growth factor (HGF) expressions in the angiogenesis and metastasis of gastric cancer (GC). From May 2012 to December 2015, 110 GC patients who received surgical treatment in the First Hospital of Qinhuangdao were selected. The HGF and FAP expressions in 110 cases of GC, 130 cases of normal gastric mucosa and 115 cases of gastric ulcer were detected by streptavidin-perosidase (SP) method. Venous blood HGF level of GC patients was tested by enzyme-linked immunosorbent assay (ELISA). The micro-vessel number of the patients in the three groups were calculated and analyzed. In GC group, positive expression rates of FAP and HGF protein were 61.8% and 67.3% respectively, which were both higher than those in normal gastric mucosa and gastric ulcer groups. The micro-vessel numbers in patients of the normal gastric mucosa and gastric ulcer groups are far less than that in GC group. FAP, HGF and micro-vessel density (MVD) were significantly correlated with infiltration depth, tumor-node-metastasis (TNM) staging, lymph node metastasis (LNM) and distant metastasis. The results of ELISA showed that serum HGF level was related to tumor size, infiltration degree, TNM staging, LNM and distant metastasis. FAP and HGF expressions in GC were positively correlated with MVD, and the expressions of FAP and HGF in GC were in positive correlation. Our study provided evidence that high FAP and HGF expressions may be positively correlated with the angiogenesis and metastasis of GC.


Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Gelatinases/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Proteínas de Membrana/metabolismo , Neovascularização Patológica/patologia , Serina Endopeptidases/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/metabolismo , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neovascularização Patológica/metabolismo , Prognóstico , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida
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