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1.
Pest Manag Sci ; 80(3): 1474-1483, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37947785

RESUMO

BACKGROUND: The tea aphid, Toxoptera aurantia is a destructive pest causing severe damage to the quality and yield of tea, Camellia sinensis. Relying on chemical insecticides to control this pest causes adverse ecological and economic consequences. Trap plants are an eco-friendly alternative strategy to mitigate pest damage on focal plants by attracting target insects and natural enemies. Yet, the utilization of trap plants in tea plantations remains limited. Besides, the effects of the trap plant on the tea aphid-ant-predator community and tea quality and yield are unknown. RESULTS: Intercropped Flemingia macrophylla successfully trapped tea aphids and enhanced the complexity of aphid-ant-predator networks over three consecutive years compared to monoculture management. Moreover, F. macrophylla significantly increased the abundance of natural predators by 3100% and species richness by 57%. The increasing predators suppressed the aphid population and hampered its spillover to neighbouring tea plants. Consequently, F. macrophylla improved tea quality by an 8% increase in soluble sugar and a 26% reduction in polyphenols to amino acids ratio. CONCLUSION: The study illustrated that F. macrophylla is a suitable trap crop for tea aphid control in tea plantations. This legume increases species nodes and strengthens multiple connections in aphid-associated communities through its cascade effects, improving tea quality. These findings shed light on the potential application of trap plants in tea plantations as an efficient integrated pest management (IPM) strategy. © 2023 Society of Chemical Industry.


Assuntos
Afídeos , Camellia sinensis , Fabaceae , Inseticidas , Animais , Insetos , Inseticidas/farmacologia , Chá
2.
Zhongguo Fei Ai Za Zhi ; 26(7): 507-514, 2023 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-37653014

RESUMO

BACKGROUND: More early-stage non-small cell lung cancer (NSCLC) are diagnosed in time and treated surgically, but systematic lymph node dissection can not bring enough survival benefits for them, and even increase the probability of postoperative complications. This study aims to analyze the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes for NSCLC with diameter ≤2 cm, so as to provide reference for surgery. METHODS: We collected 1051 patients with pulmonary nodule diameter ≤2 cm who were treated by pulmonary lobectomy with lymph node sampling/dissection in Department of Thoracic Surgery of the First Affiliated Hospital with Nanjing Medical University from December 2009 to December 2019. SPSS 26.0 statistical software was used for statistical analysis, to explore the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes. RESULTS: 95 of 1051 (9.04%) patients presented lymph node metastasis. Male, pathological non-adenocarcinoma, 1 cm0.05). Lymph nodes in group N1 were significantly correlated with lymph node metastasis in groups #2R, #4R, #5, #6, #7 and #9 (P<0.01). CONCLUSIONS: Lobe-specific lymph node dissection (LSND) can be performed for early-stage NSCLC. Male, pathological non-adenocarcinoma, 1 cm

Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Metástase Linfática , Neoplasias Pulmonares/cirurgia
3.
J Immunol Res ; 2022: 9916228, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093435

RESUMO

Objective: This study explored the colorectal cancer exosome lncRNA prostate cancer associated transcript 1- (PCAT1) mediated circulating tumors and the mechanism of cell colorectal cancer liver metastasis. Methods: Exosomes were extracted from the primary colorectal cancer (CRC) cell lines HCT116 and SW480 and cultured with T84 and human umbilical vein endothelial (HUVE) cells. The expression of PCAT1 and miR-329-3p was detected by real-time quantitative polymerase chain reaction (RT-qPCR), the expression of Netrin-1, CD146, and epithelial mesenchymal transition (EMT) related proteins was detected by Western blot, the proliferation activity of T84 cells was detected by cell counting kit 8 (CCK-8), and cell migration was detected by Transwell. The expression of the F-actin signal was detected by immunofluorescence after coculture of exosomes with human umbilical vein endothelial cells (HUVECs). Changes in subcutaneous tumor and liver nodule size after PCAT1 deletion were observed in a mouse model of liver metastasis from rectal cancer. Results: PCAT1 expression was upregulated in primary cell lines and their exosomes. After exosomes were cocultured with colorectal cancer tumor circulating T84 cells, the expression of Netrin-1 and CD146 was upregulated, the expression of miR-329-3p was downregulated, the proliferation and migration ability of T84 cells were enhanced, and EMT occurred. After knocking down PCAT1, the above phenomenon was reversed. Similarly, after exosomes were cocultured with HUVECs, the expression of the F-actin signal increased, and after PCAT1 was knocked down, the F-actin signal also decreased. PCAT1 regulates miR-329-3p/Netrin-1 and affects the biological behavior of T84 and F-actin signal expression in HUVECs. In a mouse model of colorectal cancer liver metastasis, knocking down PCAT1 significantly reduced the nodules formed by liver metastasis in mice. Conclusions: LncRNA PCAT1 derived from colorectal cancer exosomes regulates the activity of the Netrin-1-CD146 complex in circulating tumor cells (CTCs) to promote the occurrence of colorectal cancer EMT and liver metastasis and provides new molecular targets for the treatment of colorectal cancer liver metastasis.


Assuntos
Antígeno CD146/metabolismo , Neoplasias Colorretais , Neoplasias Hepáticas , MicroRNAs , Netrina-1/metabolismo , RNA Longo não Codificante , Actinas/metabolismo , Animais , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Masculino , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase Neoplásica , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
4.
J Nat Prod ; 85(7): 1751-1762, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35703501

RESUMO

Bacteria in marine biofilms are a rich reservoir of natural products. To facilitate novel secondary metabolite discovery, we investigated the metabolic profile of a marine biofilm-derived Bacillus sp. B19-2 by combining bioinformatics and LC-UV-MS analyses. After dereplication and purification of putatively unknown compounds, a new family of compounds 1-8 was uncovered and named bathiapeptides. Structural elucidation using NMR, HRESIMS, ozonolysis, advanced Marfey's analysis, and X-ray diffraction revealed that bathiapeptides are polypeptides that contain a rare polythiazole moiety. These compounds exhibited strong cytotoxicity against Hep G2, HeLa, MCF-7, and MGC-803 cell lines, and the lowest IC50 value was 0.5 µM. An iterative biosynthesis logic in bathiapeptides' biosynthesis was proposed based on the identified chemical structures and putative gene cluster analysis.


Assuntos
Bacillus , Produtos Biológicos , Bacillus/metabolismo , Biofilmes , Produtos Biológicos/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Peptídeos/metabolismo
5.
Nat Prod Rep ; 39(5): 991-1014, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35288725

RESUMO

Covering: up to 2021Colibactin(s), a group of secondary metabolites produced by the pks island (clb cluster) of Escherichia coli, shows genotoxicity relevant to colorectal cancer and thus significantly affects human health. Over the last 15 years, substantial efforts have been exerted to reveal the molecular structure of colibactin, but progress is slow owing to its instability, low titer, and elusive and complex biosynthesis logic. Fortunately, benefiting from the discovery of the prodrug mechanism, over 40 precursors of colibactin have been reported. Some key biosynthesis genes located on the pks island have also been characterised. Using an integrated bioinformatics, metabolomics, and chemical synthesis approach, researchers have recently characterised the structure and possible biosynthesis processes of colibactin, thereby providing new insights into the unique biosynthesis logic and the underlying mechanism of the biological activity of colibactin. Early developments in the study of colibactin have been summarised in several previous reviews covering various study periods, whereas the two most recent reviews have focused primarily on the chemical synthesis of colibactin. The present review aims to provide an update on the biosynthesis and bioactivities of colibactin.


Assuntos
Mutagênicos , Policetídeos , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Mutagênicos/metabolismo , Peptídeos/química , Policetídeos/metabolismo
6.
Fitoterapia ; 158: 105160, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35182695

RESUMO

Isogeopyxins A-C (1-3), three new diterpenoids with ent-kaurane, ent-pimarane, and ent-abietane scaffolds, respectively, along with six known ent-kauranoids, were isolated from the fermentation culture of Geopyxis sp. XY93 inhabiting the leaves of Isodon parvifolia. Their structures were elucidated by interpretation of spectroscopic data, and single crystal X-ray diffraction. It marks the first time that ent-kauranoids, characteristic metabolites of Isodon species, have been isolated from an associated endophytic fungus.


Assuntos
Antineoplásicos Fitogênicos , Ascomicetos , Diterpenos do Tipo Caurano , Diterpenos , Isodon , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Isodon/química , Estrutura Molecular
8.
Aging (Albany NY) ; 13(10): 14198-14218, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34016787

RESUMO

We investigated the role of long non-coding RNA (lncRNA) LOC146880 in esophageal squamous cell carcinoma (ESCC). LOC146880 was significantly upregulated in ESCC tissues (n = 21) and cell lines compared to the corresponding controls. Higher LOC146880 expression correlated with poorer overall survival (OS) of ESCC patients. Moreover, CREB-binding protein (CBP) and H3K27 acetylation levels were significantly higher in the LOC146880 promoter in ESCC cell lines than in the controls. LOC146880 silencing inhibited in vitro proliferation, invasion, migration, and epithelial-mesenchymal transition of ESCC cells. LOC146880 silencing also induced G1-phase cell cycle arrest and apoptosis in ESCC cells. Bioinformatics analysis, dual luciferase reporter assays, and RNA immunoprecipitation assays showed that LOC146880 regulates FSCN1 expression in ESCC cells by sponging miR-328-5p. Moreover, FSCN1 expression correlated with activation of the MAPK signaling pathway in ESCC cells and tissues. In vivo xenograft tumor volume and liver metastasis were significantly reduced in nude mice injected with LOC146880-silenced ESCC cells as compared to those injected with control shRNA-transfected ESCC cells. These findings show that the LOC146880/miR-328-5p/FSCN1/MAPK axis regulates ESCC progression in vitro and in vivo. LOC146880 is thus a promising prognostic biomarker and potential therapeutic target in ESCC.


Assuntos
Proteínas de Transporte/metabolismo , Progressão da Doença , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , RNA Longo não Codificante/metabolismo , Acetilação , Sequência de Bases , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Lisina/metabolismo , Proteínas dos Microfilamentos/genética , Fragmentos de Peptídeos/metabolismo , RNA Longo não Codificante/genética , Sialoglicoproteínas/metabolismo , Transcrição Gênica
9.
Front Microbiol ; 12: 635268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33633715

RESUMO

The crude extract of Streptomyces chrestomyceticus exhibited strong and broad activities against most "ESKAPE pathogens." We conducted a comprehensive chemical investigation for secondary metabolites from the S. chrestomyceticus strain and identified two novel albofungin (alb) derivatives, i.e., albofungins A (1) and B (2), along with two known compounds, i.e., albofungin (3) and chloroalbofungin (4). The chemical structures of the novel compounds were elucidated using HRMS, 1D and 2D NMR, and electronic circular dichroism spectroscopy. The draft genome of S. chrestomyceticus was sequenced, and a 72 kb albofungin (alb) gene cluster with 72 open reading frames encoding type II polyketide synthases (PKSs), regulators, and transporters, and tailoring enzymes were identified using bioinformatics analysis. The alb gene cluster was confirmed using the heterologous expression in Streptomyces coelicolor, which successfully produced the compounds 3 and 4. Furthermore, compounds 1-4 displayed remarkable activities against Gram-positive bacteria and antitumor activities toward various cancer cells. Notably, compounds 1 and 3 showed potent activities against Gram-negative pathogenic bacteria. The terminal deoxynucleotidyl transferase (dUTP) nick-end labeling and flow cytometry analysis verified that compound 1 inhibited cancer cell proliferation by inducing cellular apoptosis. These results indicated that albofungins might be potential candidates for the development of antibiotics and antitumor drugs.

10.
Expert Rev Gastroenterol Hepatol ; 15(4): 437-446, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33121317

RESUMO

Background: This study aimed to develop nomograms predicting the overall survival (OS) of patients younger than 50 years old with esophageal cancer.Methods: We selected patients included 2004-2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed using significant variables from multivariable Cox analyses. The discrimination and calibration power of the models were evaluated using concordance indexes (C-indexes) and calibration curves. Decision curve analysis was used to assess the clinical net benefits of the nomograms.Results: Of 1,997 selected patients, 53.2% had advanced-stage tumor. Race, grade, T stage, N stage, and treatment were independent factors affecting OS in early-stage patients. The C-indexes of the corresponding nomogram were 0.710 (95% CI = 0.684-0.736) and 0.681 (95% CI = 0.640-0.722) in training and validation sets, respectively. Grade, marital status, and treatment were independent factors affecting OS in advanced-stage patients. The C-indexes of the corresponding nomogram were 0.677 (95% CI = 0.653-0.701) and 0.675 (95% CI = 0.638-0.712) in training and validation sets, respectively. Calibration curves demonstrated high consistency between predicted and actual survival.Conclusion: We constructed and verified nomograms that could accurately predict the survival rate of esophageal cancer in patients younger than 50 years old. This may help clinicians better understand prognostic factors.


Assuntos
Técnicas de Apoio para a Decisão , Neoplasias Esofágicas/epidemiologia , Nomogramas , Adolescente , Adulto , Idade de Início , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Feminino , Humanos , Incidência , Masculino , Estado Civil , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Fatores Raciais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Programa de SEER , Estados Unidos , Adulto Jovem
11.
Chin Med J (Engl) ; 133(21): 2532-2542, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-32947363

RESUMO

BACKGROUND: Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis. METHODS: The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays. RESULTS: Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs. CONCLUSION: The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Biomarcadores , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Curva ROC
12.
J Cancer ; 11(7): 1985-1993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194810

RESUMO

Cancer-testis (CT) genes played important roles in the progression of malignant tumors and were recognized as promising therapeutic targets. However, the roles of genetic variants in CT genes in lung cancer susceptibility have not been well depicted. This study aimed to evaluate the associations between genetic variants in CT genes and lung cancer risk in Chinese population. A total of 22,556 qualified SNPs from 268 lung cancer associated CT genes were initially evaluated based on our previous lung cancer GWAS (Genome-wide association studies) with 2,331 cases and 3,077 controls. As a result, 17 candidate SNPs were further genotyped in 1,056 cases and 1,053 controls using Sequenom platform. Two variants (rs6941653, OPRM1, T > C, screening: OR = 1.24, 95%CI: 1.12-1.38, P = 2.40×10-5; validation: OR = 1.18, 95%CI: 1.01-1.37, P = 0.039 and rs402969, NLRP8, C > T, screening: OR = 1.15, 95%CI: 1.04-1.26, P = 0.006; validation: OR = 1.16, 95%CI: 1.02-1.33, P = 0.028) were identified as novel lung cancer susceptibility variants. Stratification analysis indicated that the effect of rs6941653 was stronger in lung squamous cell carcinoma (OR = 1.36) than that in lung adenocarcinoma (OR = 1.15, I2 = 77%, P = 0.04). Finally, functional annotations, differential gene expression analysis, pathway and gene ontology analyses were performed to suggest the potential functions of our identified variants and genes. In conclusion, this study identified two novel lung cancer risk variants in Chinese population and provided deeper insight into the roles of CT genes in lung tumorigenesis.

13.
Biochem Biophys Res Commun ; 525(2): 303-307, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32089263

RESUMO

Microtubules are involved in celluar processes of movement, intracellular trafficking and mitosis, thus microtubule-targeting agents have been widely used in cancer therapy. Herein, we report isopenicin A, a novel meroterpenoid isolated from the plant endophytic fungus of Penicillium sp. sh18, as a novel microtubule binding molecule that efficiently depolymerizes microtubule polymerization to evoke G2/M cell cycle arrest and subsequent cell apoptosis, contributing to proliferation inhibition of human tumor cell lines. The discovery of isopenicin A provides a new chemotype for discovery and development of promising microtubule inhibitors.


Assuntos
Antineoplásicos/isolamento & purificação , Penicillium/química , Moduladores de Tubulina/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Microtúbulos/metabolismo , Polimerização/efeitos dos fármacos , Terpenos/isolamento & purificação , Terpenos/farmacologia , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia
14.
J Cell Physiol ; 235(3): 3043-3055, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31544245

RESUMO

Esophageal cancer (EC) is the world's eighth most common malignant neoplasm and is ranked as the sixth leading cause of death related to cancer. Aberrant microRNA (miRNA) expression has been reported to be associated with esophageal squamous cell carcinoma. However, the molecular mechanism of miR-204-5p in esophageal squamous cell carcinoma (ESCC) is not clear. Therefore, the aim of this study was to investigate the potential role of miR-204-5p in ESCC. In the present study, we found that miR-204-5p could affect ESCC proliferation, invasion, apoptosis, and cell cycle in cell and mouse models. A dual-luciferase reporter assay showed that miR-204-5p expression was negatively correlated with interleukin-11 (IL-11) expression. IL-11 overexpression reversed the suppressive effects of miR-204-5p in the cell lines. These results indicated that miR-204-5p functions as a tumor suppressor by directly targeting IL-11 in ESCC.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Carcinoma de Células Escamosas do Esôfago/genética , Interleucina-11/metabolismo , MicroRNAs/genética , Proliferação de Células/fisiologia , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Interleucina-11/genética , Neoplasias Bucais/genética , Invasividade Neoplásica/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
15.
Clin Sci (Lond) ; 133(20): 2085-2105, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31654063

RESUMO

A previous study reported that histone methyltransferase SETD3 is up-regulated in tumor tissues of hepatocellular carcinoma (HCC) and is associated with the growth of HCC. However, the clinical significance and the effect of SETD3 on HCC metastasis remain unclear. In the present study, both the protein and mRNA expression levels of SETD3 were measured in a larger cohort of HCC patients. The results showed that the protein level of SETD3 in HCC tissues was significantly higher than that in non-tumorous tissues, which was inconsistent with the mRNA expression level of SETD3. The high protein level of SETD3 in HCC tissues was significantly associated with male gender, poor pathological differentiation, liver cirrhosis and unfavorable prognosis of HCC patients. Subsequently, we demonstrated that SETD3 could be regulated at post-transcriptional step by a couple of miRNAs (miR-16, miR-195 and miR-497). Additionally, in vitro and in vivo experiments revealed that SETD3 played opposing roles in proliferation and metastasis of HCC: promoting proliferation but inhibiting metastasis. Mechanistic experiments revealed that doublecortin-like kinase 1 (DCLK1) was a downstream target of SETD3. SETD3 could increase the DNA methylation level of DCLK1 promoter to inhibit the transcription of DCLK1. Further study revealed that DCLK1/PI3K/matrix metalloproteinase (MMP) 2 (MMP-2) was an important pathway that mediated the effect of SETD3 on HCC metastasis. In conclusion, the present study revealed that SETD3 is associated with tumorigenesis and is a promising biomarker for predicting the prognosis of HCC patients after surgical resection. In addition, SETD3 plays inhibitory role in HCC metastasis partly through DCLK1/PI3K/MMP-2 pathway.


Assuntos
Carcinoma Hepatocelular/genética , Histona Metiltransferases/genética , Neoplasias Hepáticas/genética , Idoso , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/cirurgia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Metilação de DNA/genética , Quinases Semelhantes a Duplacortina , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Hepatectomia , Histona Metiltransferases/deficiência , Histona Metiltransferases/metabolismo , Histona Metiltransferases/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Processamento Pós-Transcricional do RNA , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Células Tumorais Cultivadas , Regulação para Cima
16.
Onco Targets Ther ; 12: 8047-8053, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632058

RESUMO

BACKGROUND: Long non-coding RNS (lncRNA) GATA6-AS regulates endothelial cell growth, which is involved in many types of human diseases. PURPOSE: Our study was carried out to investigate the involvement of GATA6-AS in gallbladder cancer (GBC). PATIENTS AND METHODS: Sixty-two patients with GBC were recruited in this study. PCR analysis was performed to determine the expression of GATA6-AS, miR-421 and TIMP-2 in tissues or cell lines. Transwell migration and invasion assay was applied. RESULTS: We found that GATA6-AS was downregulated in tumor tissues than in adjacent healthy tissues of GBC patients, and GATA6-AS expression levels in tumor tissues decreased with the increase of clinical stages. MiR-421 was upregulated in tumor tissues than in adjacent healthy tissues of GBC patients and was inversely correlated with the expression levels of GATA6-AS. MiR-421 overexpression failed to significantly affect GATA6-AS in GBC cells, while GATA6-AS overexpression resulted in inhibited miR-421 expression. GATA6-AS overexpression led to decreased migration and invasion rates of GBC cells. MiR-421 overexpression led to increased migration and invasion rates of GBC. Rescue experiments (co-transfection) showed that miR-421 overexpression led to attenuated effects of GATA6-AS overexpression. CONCLUSION: GATA6-AS may inhibit cancer cell migration and invasion in GBC by downregulating miR-421.

17.
Eur Arch Otorhinolaryngol ; 276(4): 957-968, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30747316

RESUMO

BACKGROUND: The prognostic value of microRNA-375 (miR-375) expression in squamous cell carcinoma (SCC) had been reported in the previous studies; however, the results remain inconsistent. This study was performed to investigate the prognostic significance of miR-375 expression in SCC based on all eligible evidences. METHODS: Relevant studies were identified by searching PubMed, Embace, Medline, Cochrane Library, and China Biology Medicine disk. Survival outcome including overall survival (OS) and other survival outcomes were used as the primary endpoint to evaluate the prognostic outcome of patients with SCC. All statistical analyses were performed in RevMan software version 5.3 and STATA software version 14.1. Furthermore, the quality of included studies was assessed by The Newcastle-Ottawa Scale. RESULTS: In total, 13 studies, including 1340 patients, met the inclusion criteria for our meta-analysis. The pooled analysis results indicated that downregulation of miR-375 significantly predicted poor OS (HR 1.58, 95% CI 1.34-1.88, P < 0.001). Downregulated miR-375 was also correlated with the other survival outcomes. Subgroup analysis based on tumor type found that lower expression of miR-375 was significantly related with poor OS in patients with esophageal squamous cell carcinoma (ESCC) (HR 1.58, 95% CI 1.29-1.94, P < 0.001) and head and neck squamous cell carcinoma (HNSCC) (HR 1.59, 95% CI 1.16-2.18, P = 0.004). CONCLUSIONS: This meta-analysis demonstrated that the downexpression of miR-375 was significantly correlated with poor OS in patients with SCCs and indicated the potential clinical use of miR-375 as a molecular biomarker, particularly in assessing prognosis for patients with ESCC and HNSCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , MicroRNAs/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Biomarcadores Tumorais/genética , Regulação para Baixo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
18.
Org Lett ; 21(3): 771-775, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640477

RESUMO

Isopenicins A-C (1-3), three novel meroterpenoids possessing two types of unprecedented terpenoid-polyketide hybrid skeletons, were isolated from the cultures of Penicillium sp. sh18. Their structures were determined through synergetic use of extensive spectroscopic analysis, quantum-chemical calculation with ANN-PRA analysis, and X-ray crystallographic analysis. Additionally, the inhibitory activities of these compounds on the Wnt/ß-catenin signaling pathway were evaluated, and 1 was identified as a potent inhibitor of the Wnt signaling pathway.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Endófitos/química , Penicillium/química , Terpenos/química , Terpenos/farmacologia , Células HEK293 , Humanos , Modelos Moleculares , Conformação Molecular , Via de Sinalização Wnt/efeitos dos fármacos
19.
Cancer Epidemiol Biomarkers Prev ; 28(5): 867-881, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30602498

RESUMO

Acting as an important tumor-related miRNA, the clinical significance and underlying mechanisms of miR-145 in various malignant tumors have been investigated by numerous studies. This study aimed to comprehensively estimate the prognostic value and systematically illustrate the regulatory mechanisms of miR-145 based on all eligible literature.Relevant studies were acquired from multiple online databases. Overall survival (OS) and progression-free survival (PFS) were used as primary endpoints. Detailed subgroup analyses were performed to decrease the heterogeneity among studies and recognize the prognostic value of miR-145. All statistical analyses were performed with RevMan software version 5.3 and STATA software version 14.1. A total of 48 articles containing 50 studies were included in the meta-analysis. For OS, the pooled results showed that low miR-145 expression in tumor tissues was significantly associated with worse OS in patients with various tumors [HR = 1.70; 95% confidence interval (CI), 1.46-1.99; P < 0.001). Subgroup analysis based on tumor type showed that the downregulation of miR-145 was associated with unfavorable OS in colorectal cancer (HR = 2.17; 95% CI, 1.52-3.08; P < 0.001), ovarian cancer (HR = 2.15; 95% CI, 1.29-3.59; P = 0.003), gastric cancer (HR = 1.78; 95% CI, 1.35-2.36; P < 0.001), glioma (HR = 1.65; 95% CI, 1.30-2.10; P < 0.001), and osteosarcoma (HR = 2.28; 95% CI, 1.50-3.47; P < 0.001). For PFS, the pooled results also showed that the downregulation of miR-145 was significantly associated with poor PFS in patients with multiple tumors (HR = 1.39; 95% CI, 1.16-1.67; P < 0.001), and the subgroup analyses further identified that the low miR-145 expression was associated with worse PFS in patients with lung cancer (HR = 1.97; 95% CI, 1.25-3.09; P = 0.003) and those of Asian descent (HR = 1.50; 95% CI, 1.23-1.82; P < 0.001). For the regulatory mechanisms, we observed that numerous tumor-related transcripts could be targeted by miR-145-5p or miR-145-3p, as well as the expression and function of miR-145-5p could be regulated by multiple molecules.This meta-analysis indicated that downregulated miR-145 in tumor tissues or peripheral blood predicted unfavorable prognostic outcomes for patients suffering from various malignant tumors. In addition, miR-145 was involved in multiple tumor-related pathways and the functioning of significant biological effects. miR-145 is a well-demonstrated tumor suppressor, and its expression level is significantly correlated with the prognosis of patients with multiple malignant tumors.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias/patologia , Humanos , Neoplasias/genética , Neoplasias/terapia , Prognóstico , Transdução de Sinais , Taxa de Sobrevida
20.
Medicine (Baltimore) ; 97(29): e11400, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30024511

RESUMO

In 2014, Joensuu and colleagues devised the first recurrence risk score (RRS) to identify the risk factors for gastrointestinal stromal tumor (GIST) recurrence. However, there are scarce data available on RRS effectiveness and efficiency. Therefore, we retrospectively analyzed clinical data to validate Joensuu's RRS in patients treated with adjuvant imatinib.In this retrospective cohort study, data were collected from patients with GIST who were treated with adjuvant imatinib between December 2005 and May 2017 in the West China Hospital. The study consisted of 137 patients, after application of inclusion and exclusion criteria. Recurrence-free survival (RFS) was the primary end point.The RRSs for 137 patients were divided into 3 groups: low (n = 46), medium (n = 48), and high (n = 43). The RFSs of the 3 groups were significantly different (P < .001). In patients who received adjuvant imatinib for <36 months, the RFS difference was also significant (P < .001), and the result was similar in patients treated with adjuvant imatinib for ≥36 months (P = .03). The area under the curve of the RRS was 0.84 ([95% confidence interval] 0.76-0.92, P < .001), suggesting that the RRS method could accurately assess recurrence risks for patients with GIST who were treated with adjuvant imatinib.It is appropriate to apply the RRS method to assess recurrence risks for patients with GIST who were treated with adjuvant imatinib. A longer adjuvant imatinib duration is recommended for high-risk patients with GIST. It is also important to identify a more effective treatment for patients who are resistant to imatinib.


Assuntos
Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/patologia , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/patologia , Adjuvantes Imunológicos/uso terapêutico , Adulto , Idoso , Área Sob a Curva , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
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