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1.
Phytother Res ; 34(7): 1629-1637, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32067269

RESUMO

Curcumin (CUR) is a kind of polyphenolic compound and widely used in the treatment of diseases. However, the involvement of CUR in thymic carcinoma remains unknown. The object of our research is to clarify the role of CUR and related regulatory mechanism in thymic carcinoma cells. After treatment with CUR for 24 hr, cell viability, apoptosis, migration, and invasion of TC1889 cells were measured. Real-time polymerase chain reaction was executed to examine the expression of microRNA-27a (miR-27a) in thymic carcinoma tissues and TC1889 cells. After miR-27a mimic transfection, whether miR-27a is involved in CUR-modulated cell behaviors was measured. Finally, western blot was utilized to detect mTOR and Notch 1 pathways-linked proteins. CUR restrained cell viability and increased cell apoptosis of TC1889 cells. In addition, cell migration and invasion were restrained by CUR. Meanwhile, miR-27a expression was positively regulated in thymic carcinoma tissues and downregulated by CUR in TC1889 cells. Overexpressed miR-27a reversed the CUR-induced reduction of growth, migration, and invasion in TC1889 cells. Furthermore, CUR blocked mTOR and Notch 1 pathways via downregulating miR-27a. We demonstrated that CUR blocked mTOR and Notch 1 pathways via downregulating miR-27a, thereby suppressing cell growth, migration, and invasion of thymic carcinoma cells.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Curcumina/uso terapêutico , Neoplasias do Timo/tratamento farmacológico , Adulto , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Curcumina/farmacologia , Regulação para Baixo , Humanos , Pessoa de Meia-Idade , Transfecção
2.
Clin Lab ; 64(6): 895-900, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945332

RESUMO

BACKGROUND: Our previous studies revealed that concentrations of circulating antibodies to annexin A1 (ANXA1) were increased in non-small lung cancer (NSCLC). This study was thus designed to replicate this initial finding with an independent sample set. METHODS: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to examine plasma antiANXA1 IgG levels in 220 patients with NSCLC and 200 control subjects. RESULTS: Mann-Whitney U test showed that patients with NSCLC had significantly higher anti-ANXA1 IgG levels than control subjects (Z = -4.02, p < 0.001); male patients appeared to mainly contribute to the increased antibody level (Z = -3.09, p = 0.002). Receiver operating characteristic (ROC) curve analysis showed an overall area under the ROC curve (AUC) of 0.61 (95% CI: 0.56 - 0.67), with sensitivity of 8% against a specificity of 95.0%. Spearman's correlation analysis failed to show a significant correlation between the anti-ANXA1 IgG levels and the expression of three tumor-associated antigens including p53 (r = 0.156, p = 0.027), Ki67 (r = -0.048, p = 0.489), and EGFR (r = 0.02, p = 0.782). CONCLUSIONS: Increased levels of circulating anti-ANXA1 IgG antibody may have a prognostic value for NSCLC.


Assuntos
Anexina A1/imunologia , Anticorpos Anti-Idiotípicos/imunologia , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Idoso , Anticorpos Anti-Idiotípicos/sangue , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC
3.
Sensors (Basel) ; 17(7)2017 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-28677619

RESUMO

BeiDou system navigation messages are modulated with a secondary NH (Neumann-Hoffman) code of 1 kbps, where frequent bit transitions limit the coherent integration time to 1 millisecond. Therefore, a bit synchronization algorithm is necessary to obtain bit edges and NH code phases. In order to realize bit synchronization for BeiDou weak signals with large frequency deviation, a bit synchronization algorithm based on differential coherent and maximum likelihood is proposed. Firstly, a differential coherent approach is used to remove the effect of frequency deviation, and the differential delay time is set to be a multiple of bit cycle to remove the influence of NH code. Secondly, the maximum likelihood function detection is used to improve the detection probability of weak signals. Finally, Monte Carlo simulations are conducted to analyze the detection performance of the proposed algorithm compared with a traditional algorithm under the CN0s of 20~40 dB-Hz and different frequency deviations. The results show that the proposed algorithm outperforms the traditional method with a frequency deviation of 50 Hz. This algorithm can remove the effect of BeiDou NH code effectively and weaken the influence of frequency deviation. To confirm the feasibility of the proposed algorithm, real data tests are conducted. The proposed algorithm is suitable for BeiDou weak signal bit synchronization with large frequency deviation.

4.
Tumour Biol ; 35(12): 12635-43, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25213696

RESUMO

Accumulating evidence has suggested that concentrations of blood-based circulating micro-ribonucleic acids (microRNAs, miRNAs) in breast tumor patients are significantly higher/lower than that in normal individuals, indicating that circulating miRNAs may serve as novel blood-based biomarkers for breast tumor. However, the results of previous studies on this issue have been inconclusive. Therefore, we perform a meta-analysis to determine whether aberrant miRNA expression can be used as molecular markers in blood for the diagnosis of breast tumor. PubMed and other databases were searched to identify eligible studies. The sensitivity and specificity were used to plot the summary receiver operator characteristic curve and calculate the area under the curve (AUC). Finally, 15 articles with a total of 1,428 breast tumor patients and 952 healthy individuals were involved. The summary estimates revealed that the pooled sensitivity was 76 % with 95 % confidence interval (CI) of 67-83 %; the specificity was 87 % with 95 % CI of 77-93 %; the PLR was 5.9 with 95 % CI of 3.3-10.4; the NLR was 0.28 with 95 % CI of 0.20-0.39; the DOR was 21 with 95 % CI of 10-44; and the AUC was 0.88 with 95 % CI of 0.84-0.90. The most noteworthy is that multiple-miRNA assay displayed a better diagnostic performance than single-miRNA assay. In summary, the results of the present meta-analysis suggested that blood-based miRNAs may serve as novel molecular biomarkers for breast tumor, with a relative high level of accuracy, especially based on multiple-miRNA assay. Further large-scale prospective studies are necessary to validate their potential applicability for breast tumor prognosis, treatment, and surveillance.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , MicroRNAs/genética , Biomarcadores Tumorais , Feminino , Humanos , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Adv Sci (Weinh) ; 10(11): e2206264, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36782337

RESUMO

Engineered cardiac tissues (ECTs) derived from human induced pluripotent stem cells (hiPSCs) are viable alternatives for cardiac repair, patient-specific disease modeling, and drug discovery. However, the immature state of ECTs limits their clinical utility. The microenvironment fabricated using 3D scaffolds can affect cell fate, and is crucial for the maturation of ECTs. Herein, the authors demonstrate an electric-field-driven (EFD) printed 3D highly ordered microstructure with cell feature size to promote the maturation of ECTs. The simulation and experimental results demonstrate that the EFD jet microscale 3D printing overcomes the jet repulsion without any prior requirements for both conductive and insulating substrates. Furthermore, the 3D highly ordered microstructures with a fiber diameter of 10-20 µm and spacing of 60-80 µm have been fabricated by maintaining a vertical jet, achieving the largest ratio of fiber diameter/spacing of 0.29. The hiPSCs-derived cardiomyocytes formed ordered ECTs with their sarcomere growth along the fiber and developed synchronous functional ECTs inside the 3D-printed scaffold with matured calcium handling compared to the 2D coverslip. Therefore, the EFD jet 3D microscale printing process facilitates the fabrication of scaffolds providing a suitable microenvironment to promote the maturation of ECTs, thereby showing great potential for cardiac tissue engineering.


Assuntos
Células-Tronco Pluripotentes Induzidas , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Miócitos Cardíacos , Diferenciação Celular , Impressão Tridimensional
6.
Front Surg ; 9: 1088142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684371

RESUMO

Branchial cleft cysts are congenital diseases of the neck caused by abnormal embryonic development of the first to fourth branchial clefts. Most branchial cleft cysts are found in the head and neck, but branchial cleft cysts arising in posterior mediastinum are rarely reported. We report a 44-year-old Chinese man who was found to have a right-posterior mediastinal mass on chest computed tomography (CT) during a physical examination. The size of the mass was about 30.6 mm * 25.1 mm and enhanced CT of the chest showed an occupying lesion in the right parietal esophagus of the upper-posterior mediastinum with no significant enhancement. The patient was considered to have a neurogenic tumor with cystic change and underwent posterior mediastinal tumor resection. Postoperatively, pathological examination confirmed the final diagnosis of bronchial cleft cyst. The patient was discharged on the 7th day after surgery. One year postsurgery, no obvious recurrence was found in reexamination.

7.
Bioengineered ; 13(6): 14472-14488, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-36694453

RESUMO

Accumulating evidence have proved the key role of long non-coding RNA in lung adenocarcinoma (LUAD) progression. Bioinformatics analysis is used to seek the differentially expressed lncRNA LINC01270 from TCGA database. The overexpression of LINC01270 was then verified in LUAD tumor tissues and cell lines by qRT-PCR. LINC01270 knockdown resulted in impaired cell proliferative and invasive ability via CCK-8 assay, EdU assay, colony formation assay, transwell assay, while aberrant upregulation of LINC01270 led to enhanced cell growth and invasion. Moreover, LINC01270 was found inhibiting miR-326 and thereby overexpressing the abundance of LARP1 to promote LUAD development via PI3K/AKT pathway. It was also proved that LINC01270 knockdown could suppress LUAD tumor growth in vivo. All of these findings demonstrate thatLINC01270 is a tumor promotor in LUAD via enhancing LARP1 expressed by sponging miR-326 to facilitate the development of LUAD. LINC01270 play a significant role in LUAD, which could serve as biomarkers for early diagnosis and a novel targeted remedy.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases , Neoplasias Pulmonares/patologia , Proliferação de Células/genética , Pulmão/patologia , Adenocarcinoma/genética
8.
Cancers (Basel) ; 14(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36230685

RESUMO

Deep learning has been applied in precision oncology to address a variety of gene expression-based phenotype predictions. However, gene expression data's unique characteristics challenge the computer vision-inspired design of popular Deep Learning (DL) models such as Convolutional Neural Network (CNN) and ask for the need to develop interpretable DL models tailored for transcriptomics study. To address the current challenges in developing an interpretable DL model for modeling gene expression data, we propose a novel interpretable deep learning architecture called T-GEM, or Transformer for Gene Expression Modeling. We provided the detailed T-GEM model for modeling gene-gene interactions and demonstrated its utility for gene expression-based predictions of cancer-related phenotypes, including cancer type prediction and immune cell type classification. We carefully analyzed the learning mechanism of T-GEM and showed that the first layer has broader attention while higher layers focus more on phenotype-related genes. We also showed that T-GEM's self-attention could capture important biological functions associated with the predicted phenotypes. We further devised a method to extract the regulatory network that T-GEM learns by exploiting the attributions of self-attention weights for classifications and showed that the network hub genes were likely markers for the predicted phenotypes.

9.
Zhongguo Zhong Yao Za Zhi ; 36(4): 425-8, 2011 Feb.
Artigo em Zh | MEDLINE | ID: mdl-21598533

RESUMO

OBJECTIVE: To explore the best pretreatment condition of inorganic salting on volatile oil-bearing water body of Notopterygii Rhizoma et Radix before membrane separation. METHOD: The simulative system of volatile oil-bearing water body of Notopterygii Rhizoma et Radix was pre-treated before membrane separation by salting. The best conditions of salting were determined by selecting types and amounts of inorganic salt as investigate factors and comparing membrane flux and oil retention rate. RESULT: The best pretreatment condition of inorganic salting on volatile oil-bearing water body of Notopterygii Rhizoma et Radix before membrane separation was to add 2% sodium chloride (NaCl) according to the amount of oil-bearing water body. Gas chromatographic fingerprint showed that inorganic salting did not affect the active ingredient of volatile oil. CONCLUSION: Adding NaCl to volatile oil-bearing water body of Notopterygii Rhizoma et Radix before membrane separation can optimize membrane processes by improving membrane flux.


Assuntos
Apiaceae/química , Óleos Voláteis/isolamento & purificação , Cloreto de Sódio/farmacologia
10.
Zhongguo Zhong Yao Za Zhi ; 36(1): 41-4, 2011 Jan.
Artigo em Zh | MEDLINE | ID: mdl-21473150

RESUMO

OBJECTIVE: To separate essential oil of Caryophyllix flos from oil-in-water emulsion, and to enrich the essential oil by microfiltration (MF). METHOD: Using membrane flux and removal rate of COD as the indicatrixes, the membrane material as well as the operating conditions containing pressure, surface speed, temperature were optimized. RESULT: The results showed that QWLM membrane of hydrophilic is the proper membrane, and the best operating conditions was at 0.06 MPa, 60 degrees C, and 150 r min(-1) stir speed. CONCLUSION: It can be concluded that MF is a reasonable way to enrich essential oil of C. flox.


Assuntos
Filtração/métodos , Óleos Voláteis/isolamento & purificação , Óleos de Plantas/isolamento & purificação , Syzygium/química , Emulsões/química , Filtração/instrumentação , Membranas Artificiais , Óleos Voláteis/química , Óleos de Plantas/química
11.
Zhongguo Zhong Yao Za Zhi ; 36(19): 2653-5, 2011 Oct.
Artigo em Zh | MEDLINE | ID: mdl-22242423

RESUMO

OBJECTIVE: To study on the separation from essential oil-in-water emulsion of Citri Reticulatae Pericarpium Viride by ultrafiltration and acetoacetate extraction methods respectively, and the comparison of the oil yields and chemical compositions. METHOD: Essential oil-in-water emulsion of Citri Reticulatae Pericarpium Viride was separated by ultrafiltration and acetoacetate extraction methods respectively, and the chemical compositions were analyzed and compared by GC-MS. RESULT: Ultrafiltration method could enrich essential oil more and its chemical compositions were more similar to the essential oil prepared by steam distillation method. CONCLUSION: Ultrafiltration method is a good medium to separate essential oil from essential oil-in-water emulsion of Citri Reticulatae Pericarpium Viride.


Assuntos
Fracionamento Químico/métodos , Citrus/química , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Ultrafiltração/métodos , Emulsões , Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis/análise , Extratos Vegetais/análise
12.
Zhongguo Zhong Yao Za Zhi ; 35(17): 2273-6, 2010 Sep.
Artigo em Zh | MEDLINE | ID: mdl-21137336

RESUMO

OBJECTIVE: To explore the correlation between physical and chemical parameters of oil-bearing water bodies and ultrafiltration flux in the four simulative system of traditional Chinese medicine ( TCM) volatile oil. METHOD: Four simulative systems of TCM oil-bearing water bodies such as Tsao-ko Amomum Fruit were selected as the experimental subjects. The membrane separating under the best conditions was carried out, membrane flux, physical and chemical parameters of stock solution and permeate were collected, and SPSS computer software was used for data processing. RESULT: The membrane separation significantly changed the physical and chemical properties of oil-bearing water bodies, resulted in lower electrical conductivity and turbidity and pH value increased; Physical and chemical parameters also affected the membrane process significantly, and the flux varied with the electrical conductivity, pH, turbidity and viscosity. CONCLUSION: There is significant correlation between physical and chemical parameters of oil-bearing water bodies and their ultrafiltration flux in the four simulative systems of TCM volatile oil.


Assuntos
Medicamentos de Ervas Chinesas/química , Óleos Voláteis/química , Ultrafiltração/métodos , Fenômenos Químicos , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicina Tradicional Chinesa , Membranas Artificiais , Óleos Voláteis/isolamento & purificação , Ultrafiltração/instrumentação
13.
Cell Cycle ; 19(17): 2139-2147, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32779548

RESUMO

Traditionally, circular RAN hsa_circ_0008035 was proven to function as a tumor inhibitor in gastric cancer. Nevertheless, much less was known about hsa_circ_0008035 in osteosarcoma (OSA). This project was undertaken to assess the role of hsa_circ_0008035 in OSA. Hsa_circ_0008035 level in serum of OSA patients, OSA tissues and cell lines were measured by reverse transcription-quantitative PCR. After downregulation or overexpression of hsa_circ_0008035, cell proliferation, apoptosis and migration were tested in MG63, SAOS-2 or hFOB1.19 cells. Meanwhile, the expression level of miR-375 was analyzed. The binding between hsa_circ_0008035 and miR-375 was confirmed using bioinformatics and luciferase assay. Subsequently, the effects of miR-375 inhibition on MG63 cell growth and migratory potential were reevaluated. Eventually, the activating status of Notch pathway was assessed by Western blot. Our results demonstrated that hsa_circ_0008035 was overexpressed in serum of OSA patients, OSA tissues and cells. Silencing hsa_circRNA_0008035 impeded OSA cell growth and migration, while hsa_circ_0008035 facilitated cell behaviors of hFOB1.19 cells. Additionally, hsa_circ_0008035 negatively modulated miR-375 expression. Meanwhile, miR-375 inhibition overturned the suppressive effects of silencing hsa_circRNA_0008035 on OSA cell behaviors. Furthermore, silencing hsa_circ_0008035 perturbed Notch pathway by adjusting miR-375 expression. In conclusion, silencing hsa_circRNA_0008035 exerted repressive function on OSA cell growth and migration and Notch pathway by accelerating miR-375.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Inativação Gênica , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Circular/metabolismo , Regulação para Cima/genética , Adolescente , Sequência de Bases , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Osteossarcoma/sangue , RNA Circular/sangue , RNA Circular/genética , Receptores Notch/metabolismo , Transdução de Sinais , Adulto Jovem
14.
Can Respir J ; 2019: 9107806, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885751

RESUMO

Background: The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (NSCLC) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells. Methods: After grouping, the NCL-H1299 cells in the treatment group were treated by 10 µM XAV939 for 12 h. RNA-sequencing was performed, and then the differentially expressed circRNAs (DE-circRNAs) were analyzed by the edgeR package. Using the clusterprofiler package, enrichment analysis for the hosting genes of the DE-circRNAs was performed. Using Cytoscape software, the miRNA-circRNA regulatory network was built for the disease-associated miRNAs and the DE-circRNAs. The DE-circRNAs that could translate into proteins were predicted using circBank database and IRESfinder tool. Finally, the transcription factor (TF)-circRNA regulatory network was built by Cytoscape software. In addition, A549 and HCC-827 cell treatment with XAV939 were used to verify the relative expression levels of key DE-circRNAs. Results: There were 106 DE-circRNAs (including 61 upregulated circRNAs and 45 downregulated circRNAs) between treatment and control groups. Enrichment analysis for the hosting genes of the DE-circRNAs showed that ATF2 was enriched in the TNF signaling pathway. Disease association analysis indicated that 8 circRNAs (including circ_MDM2_000139, circ_ATF2_001418, circ_CDC25C_002079, and circ_BIRC6_001271) were correlated with NSCLC. In the miRNA-circRNA regulatory network, let-7 family members⟶circ_MDM2_000139, miR-16-5p/miR-134-5p⟶circ_ATF2_001418, miR-133b⟶circ_BIRC6_001271, and miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 regulatory pairs were involved. A total of 47 DE-circRNAs could translate into proteins. Additionally, circ_MDM2_000139 was targeted by the TF POLR2A. The verification test showed that the relative expression levels of circ_MDM2_000139, circ_CDC25C_002079, circ_ATF2_001418, and circ_DICER1_000834 in A549 and HCC-827 cell treatment with XAV939 were downregulated comparing with the control. Conclusions: Let-7 family members and POLR2A targeting circ_MDM2_000139, miR-16-5p/miR-134-5p targeting circ_ATF2_001418, miR-133b targeting circ_BIRC6_001271, and miR-221-3p/miR-222-3p targeting circ_CDC25C_002079 might be related to the mechanism in the treatment of NSCLC by XAV939.


Assuntos
Compostos Heterocíclicos com 3 Anéis/farmacologia , MicroRNAs/efeitos dos fármacos , RNA Circular/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Fator 2 Ativador da Transcrição/genética , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Análise de Sequência de RNA , Fosfatases cdc25/genética
15.
Oncol Lett ; 17(6): 4994-5004, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31186710

RESUMO

The present study aimed to reveal the key long non-coding RNAs (lncRNAs) and the potential molecular mechanisms of XAV939 treatment in non-small cell lung cancer (NSCLC). The NSCLC cell line, NCI-H1299, was cultured with 10 µM XAV939 for 12 h, and NCI-H1299 cells without XAV939 treatment were used as controls. Following RNA isolation from the two groups, RNA-sequencing was performed to detect transcript expression levels, and differentially-expressed lncRNAs (DE-lncRNAs) and DE-genes (DEGs) were identified between groups and analyzed for their functions and associated pathways. The potential associations between proteins encoded by DEGs were revealed via a protein-protein interaction (PPI) network. Subsequently, the microRNA (miRNA/miR)-mRNA, lncRNA-miRNA and lncRNA-mRNA interactions were explored, followed by competing endogenous RNA (ceRNA) network construction. A total of 396 DEGs and 224 DE-lncRNAs were identified between the XAV939 and control groups. These lncRNAs were mainly enriched in pathways such as 'ferroptosis' [DEG, solute carrier family 7 member 11 (SLC7A11)]. The PPI network consisted of 97 nodes and 112 interactions. Furthermore, a total of 10 noteworthy lncRNAs were revealed in the DE-lncRNA-DEG interaction. Finally, the lncRNA-miRNA-mRNA regulatory association, including MIR503 host gene (MIR503HG)-miR1273c-SRY-box 4 (SOX4), was explored in the current ceRNA network. The downregulation of lncRNA MIR503HG induced by XAV939 may serve an important role in NSCLC suppression via sponging miR-1273c and regulating SOX4 expression. Furthermore, the downregulation of SLC7A11 induced by XAV939 may also inhibit the development of NSCLC via the ferroptosis pathway.

16.
Sci Rep ; 9(1): 15767, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673068

RESUMO

POLE/POLD1 gene variants have been suggested as potential markers for immunotherapy due to their significant association with the tumor mutational burden (TMB), an effective indicator for response prediction in immunotherapy. However, the correlation of POLE/POLD1 variants with MSI, MMR, TMB, MMR-related and key driver gene mutations needs to be defined to support patient recruitment and therapeutic effect assessment in immunotherapy. 1,392 Chinese cancer patients were recruited, and the correlation of POLE/POLD1 variants with existing immunotherapeutic markers and cancer pathways was investigated. A next-generation sequencing panel including 605 cancer-related genes was used for variant sequencing. It was found that the frequency of POLE variants was not statistically different from that in COSMIC database, while the frequency of POLD1 variants was significantly higher in lung cancer. c.857 C > G and c.2091dupC were potential high frequency variants in Chinese cancer patients. Patients carrying POLE damaging variants were significantly younger than POLE/POLD1 WT patients. Patients carrying POLE/POLD1 damaging variants exhibited significantly higher TMB and frequency of MMR gene variants than POLE/POLD1 WT patients. Patients with POLE damaging variants also exhibited significantly higher frequency of driver gene variants than POLE/POLD1 WT patients. Further analysis showed that POLE damaging variants may affect the cancer development through MMR, TGFß and RTK/RAS/RAF signaling pathways, and POLD1 through MMR pathways. In conclusion, this study identified key characteristics and regions of POLE/POLD1 genes that correlates with TMB, MMR gene mutations and key driver gene mutations, and provided theoretical and practical basis for patient selection based on POLE/POLD1 gene status in immunotherapy.


Assuntos
DNA Polimerase III/genética , DNA Polimerase II/genética , Bases de Dados de Ácidos Nucleicos , Imunoterapia , Neoplasias Pulmonares , Mutação , Proteínas de Neoplasias/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Idoso , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade
17.
FEBS Open Bio ; 8(11): 1875-1881, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30410866

RESUMO

It has been reported that p16 protein is overexpressed in many types of solid cancer and its aberrant expression may trigger the immune response, leading to the secretion of anti-p16 antibodies. Here, we developed an in-house ELISA with three p16-derived linear peptide antigens to examine plasma anti-p16 antibody levels in patients with non-small cell lung cancer (NSCLC). Blood samples were taken from 200 control subjects and 211 patients with NSCLC prior to anticancer therapy. A Mann-Whitney U test demonstrated that plasma anti-p16a IgG levels were significantly higher in NSCLC patients than in control subjects (Z = -11.14, P < 0.001). However, neither plasma anti-p16b nor plasma anti-p16c IgG levels showed significant differences in patients with NSCLC as compared to control subjects. Moreover, further analysis indicated that anti-p16a IgG levels increased with tumor stages, and patients with late stage NSCLC, namely group IV, had the highest IgG levels among four subgroups. Receiver operating characteristic analysis revealed that the anti-p16a IgG assay had a sensitivity of 32.7% against a specificity of 95.0% in group IV, while Kaplan-Meier survival analysis revealed no significant difference in overall survival between patients with high anti-p16a IgG levels and those with low anti-p16a IgG levels (χ2  = 0.24, P = 0.63). In conclusion, anti-p16a IgG may be suitable for use as a prognostic biomarker for NSCLC.

18.
Sci Rep ; 8(1): 9847, 2018 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-29959381

RESUMO

Natural autoantibody is a key component for immune surveillance function. Regulatory T (Treg) cells play indispensable roles in promoting tumorigenesis via immune escape mechanisms. Both CD25 and FOXP3 are specific markers for Treg cells and their natural autoantibodies may be involved in anticancer activities. This work was designed to develop an in-house enzyme-linked immunosorbent assay (ELISA) to examine plasma natural IgG against CD25 and FOXP3 in non-small cell lung cancer (NSCLC). Compared with control subjects, NSCLC patients had significantly higher levels of plasma IgG for CD25a (Z = -8.05, P < 0.001) and FOXP3 (Z = -4.17, P < 0.001), lower levels for CD25b (Z = -3.58, P < 0.001), and a trend toward lower levels for CD25c (Z = -1.70, P = 0.09). Interestingly, the anti-CD25b IgG assay had a sensitivity of 25.0% against a specificity of 95.0% in an early stage patients (T1N0M0) who showed the lowest anti-CD25b IgG levels among 4 subgroups classified based on staging information. Kaplan-Meier survival analysis showed that patients with high anti-FOXP3 IgG levels had shorter survival than those with low anti-FOXP3 IgG levels (χ2 = 3.75, P = 0.05). In conclusion, anti-CD25b IgG may be a promising biomarker in terms of screening individuals at high risk of lung cancer.


Assuntos
Adenocarcinoma/sangue , Autoanticorpos/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Fatores de Transcrição Forkhead/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Neoplasias Pulmonares/sangue , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Autoanticorpos/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Prognóstico , Taxa de Sobrevida
19.
FEBS Open Bio ; 8(5): 829-835, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29744296

RESUMO

A recent study demonstrated that circulating levels of IgG antibodies against linear peptide antigens derived from baculoviral IAP repeat-containing protein 5 isoform 2 (BIRC5) and myc proto-oncogene protein (MYC) were significantly increased in nonsmall cell lung cancer (NSCLC). This study was undertaken to replicate this initial work in an independent sample. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to examine plasma IgG antibodies for three linear peptide antigens derived from BIRC5a, BIRC5b, and MYC in 211 patients with NSCLC and 200 control subjects. A Mann-Whitney U-test demonstrated that plasma anti-BIRC5a IgG levels, but not anti-BIRC5b or anti-MYC IgG levels, were significantly higher in NSCLC patients than control subjects, especially in male patients. Both squamous cell cancer and adenocarcinoma showed increased anti-BIRC5a IgG levels, but the IgG levels were not found to be changed significantly in the early stage of NSCLC. Kaplan-Meier survival analysis showed that NSCLC patients with high anti-BIRC5b IgG levels had better prognosis and longer overall survival (OS) than patients with low anti-BIRC5b IgG levels, although this significant difference failed to survive the adjustment for age, gender, NSCLC stages, and types. Plasma anti-BIRC5a and MYC IgG levels did not show significant associations with OS. In conclusion, Plasma anti-BIRC5 IgG may be a useful marker for assessment of prognosis of NSCLC but not for early diagnosis of this malignancy.

20.
Expert Rev Gastroenterol Hepatol ; 12(4): 319-329, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29451037

RESUMO

INTRODUCTION: Esophageal hiatal hernia involves abnormal abdominal entry into thoracic cavity. It is classified based on orientation between esophageal junction and diaphragm. Sliding hiatal hernia (Type-I) comprises the most frequent category, emanating from right crus of diaphragm. Type-II esophageal hernia engages both left and right muscular crura. Type-III and IV additionally include the left crus. Age and increased body mass index are key risk factors, and congenital skeletal aberrations trigger pathogenesis through intestinal malrotations. Familiar manifestations include gastric reflux, nausea, bloating, chest and epigastric discomfort, pharyngeal and esophageal expulsion and dysphagia. Weight loss and colorectal bleeding are severe symptoms. Areas covered: This review summarizes updated evidence of pathophysiology, risk factors, diagnosis and management of hiatal hernias. Laparoscopy and oesophagectomy procedures have been discussed as surgical procedures. Expert commentary: Endoscopy identifies untreatable gastric reflux; radiology is better for pre-operative assessments; manometry measures esophageal peristalsis, and CT scanning detects gastric volvulus and associated organ ruptures. Gastric reflux disease is mitigated using antacids and proton pump and histamine-2-receptor blockers. Severe abdominal penetration into chest cavity demands surgical approaches. Hence, esophagectomy has chances of post-operative morbidity, while minimally invasive laparoscopy entails fewer postoperative difficulties and better visualization of hernia and related vascular damages.


Assuntos
Esofagectomia , Hérnia Hiatal/diagnóstico , Hérnia Hiatal/terapia , Herniorrafia/métodos , Laparoscopia , Antiácidos/uso terapêutico , Esofagectomia/efeitos adversos , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/terapia , Hérnia Hiatal/epidemiologia , Hérnia Hiatal/fisiopatologia , Herniorrafia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Inibidores da Bomba de Prótons , Fatores de Risco , Resultado do Tratamento
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