Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
1.
Chem Biodivers ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519420

RESUMO

Two new oleanane-triterpenoid saponins, clinograsaponins A ( 1 ) and B ( 2 ), together with twelve known ones ( 3-14 ), were isolated from the whole herb of Clinopodium gracile (Bentham) Matsumura. Their structures were determined by spectroscopic analysis and chemical method. All the isolated compounds were evaluated for their activities against ATP-citrate lyase (ACLY) and nuclear factor kappa B (NF- κ B).

2.
Anal Chem ; 93(22): 7965-7969, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34029055

RESUMO

Probing molecular interactions is critical for screening drugs, detecting pollutants, and understanding biological processes at the molecular level, but these interactions are difficult to detect, especially for small molecules. A label-free optical imaging technology that can detect molecule binding kinetics is presented, in which free-moving particles are driven into oscillations with an alternating electrical field and the interferometric scattering patterns of the particles are imaged via an optical imaging method. By tracking the charge-sensitive variations in the oscillation amplitude with sub-nanometer precision, the small molecules and metal ions binding to the surface as well as protein-protein binding kinetics were measured. The capability of the label-free measurement of molecular interactions can provide a promising platform for screening small-molecule drugs, probing conformational changes in proteins, and detecting environmental pollutants.


Assuntos
Diagnóstico por Imagem , Proteínas , Fenômenos Biofísicos , Cinética , Ligação Proteica
3.
Phytochemistry ; 187: 112765, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33887558

RESUMO

Nine undescribed acylphloroglucinol derivatives, oblatones A-I, along with three known ones, were isolated from Syzygium oblatum. Their structures were determined on the basis of extensive spectroscopic analysis, including NMR and MS data interpretation. Oblatones A and B possess an alkylated chromanone scaffold featuring a hemiketal moiety. Oblatones C and D are the first acylphloroglucinol derivatives with an α,ß-unsaturated ketone lipid chain. Some of the isolates showed inhibitory effects on ATP citrate lyase in vitro. The binding mode of oblatone A was predicted by molecular docking.


Assuntos
Syzygium , ATP Citrato (pro-S)-Liase , Simulação de Acoplamento Molecular , Estrutura Molecular , Floroglucinol/farmacologia
4.
Environ Sci Technol ; 55(7): 4115-4122, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33566596

RESUMO

The frequent detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in healthcare environments, accommodations, and wastewater has attracted great attention to the risk of viral transmission by environmental fomites. However, the process of SARS-CoV-2 adsorption to exposed surfaces in high-risk environments remains unclear. In this study, we investigated the interfacial dynamics of single SARS-CoV-2 pseudoviruses with plasmonic imaging technology. Through the use of this technique, which has high spatial and temporal resolution, we tracked the collision of viruses at a surface and differentiated their stable adsorption and transient adsorption. We determined the effect of the electrostatic force on virus adhesion by correlating the solution and surface chemistry with the interfacial diffusion velocity and equilibrium position. Viral adsorption was found to be enhanced in real scenarios, such as in simulated saliva. This work not only describes a plasmonic imaging method to examine the interfacial dynamics of a single virus but also provides direct measurements of the factors that regulate the interfacial adsorption of SARS-CoV-2 pseudovirus. Such information is valuable for understanding virus transport and environmental transmission and even for designing anticontamination surfaces.


Assuntos
COVID-19 , SARS-CoV-2 , Fômites , Humanos
5.
Phytochemistry ; 183: 112614, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33360008

RESUMO

Six undescribed clerodane diterpenoids, dodovisins A-F, together with nine known ones, were isolated from the aerial parts of Dodonaea viscosa (L.) Jacq. Their structures were elucidated by extensive spectroscopic techniques, X-ray crystallographic analysis, and ECD calculation. Dodovisins A and B possess a rare carbon skeleton featuring a bicyclo[6.2.0]decane motif. Dodovisins C-E represent the first clerodane diterpenoids with a 4(5 â†’ 19)-abeo-2,4,10(1)-triene moiety. Dodovisins A, E, and strictic acid showed potent inhibitory activities against ATP citrate lyase.


Assuntos
Diterpenos Clerodânicos , Sapindaceae , ATP Citrato (pro-S)-Liase , Diterpenos Clerodânicos/farmacologia , Estrutura Molecular
6.
Mol Ther Nucleic Acids ; 22: 471-483, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230450

RESUMO

Although patients with non-small cell lung cancer harboring activating mutations in the epidermal growth factor receptor (EGFR) show good clinical response to EGFR tyrosine kinase inhibitors (TKIs), patients eventually develop acquired resistance. Previous studies have shown that several microRNAs (miRNAs) are involved in EGFR TKI resistance. Here, we aimed to investigate whether miR-146b-5p sensitizes the EGFR TKI-resistant lung cancer cells. Clinical analysis showed that miR-146b-5p expression in lung cancer cells isolated from pleural effusions of treatment-naive patients was significantly higher than that after acquiring resistance to EGFR TKI treatment. Ectopic expression of miR-146b-5p in EGFR TKI-resistant cells enhanced EGFR TKI-induced apoptosis. The same results were observed in EGFR-dependent and -independent osimertinib-resistant primary cancer cells (PE3479 and PE2988). Mechanically, miR-146b-5p suppressed nuclear factor κB (NF-κB) activity and NF-κB-related IL-6 and IL-8 production by targeting IRAK1. A negative correlation was observed between miR-146b-5p and IRAK1 in clinical specimens. In rescue experiments, restoration of IRAK1 expression reversed the effects of miR-146b-5p on EGFR TKI sensitivity and recovered NF-κB-regulated IL-6 and IL-8 production. In conclusion, miR-146b-5p/IRAK1/NF-κB signaling is important in promoting EGFR TKI resistance, and miR-146b-5p may be a useful tool for overcoming EGFR TKI resistance.

7.
Proc Natl Acad Sci U S A ; 117(44): 27148-27153, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33060295

RESUMO

Probing the binding between a microbe and surface is critical for understanding biofilm formation processes, developing biosensors, and designing biomaterials, but it remains a challenge. Here, we demonstrate a method to measure the interfacial forces of bacteria attached to the surface. We tracked the intrinsic fluctuations of individual bacterial cells using an interferometric plasmonic imaging technique. Unlike the existing methods, this approach determined the potential energy profile and quantified the adhesion strength of single cells by analyzing the fluctuations. This method provides insights into biofilm formation and can also serve as a promising platform for investigating biological entity/surface interactions, such as pathogenicity, microbial cell capture and detection, and antimicrobial interface screening.


Assuntos
Aderência Bacteriana/fisiologia , Análise de Célula Única/métodos , Ressonância de Plasmônio de Superfície/métodos , Biofilmes , Fenômenos Biofísicos , Técnicas Biossensoriais , Microscopia de Força Atômica , Fenômenos Físicos , Propriedades de Superfície
8.
Toxicon ; 186: 12-18, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32698025

RESUMO

The T-2 toxin exerts a variety of toxic effects on both experimental animals and humans. The integrin family plays a major role in mediating cell-ECM interactions. Therefore, the present study aimed to investigate the involvement of integrin α2ß1 in T-2 toxin-induced C28/I2 chondrocyte damage. The pathological damage of articular cartilage injury induced by T-2 toxin was observed by H&E staining. The expression levels of collagen 2 and MMP-13 (Matrix metalloproteinases 13) were detected using immunohistochemistry in articular cartilage tissues and western blotting in the cells. The blocking effect of integrin α2ß1 inhibitor on T-2 toxin-induced chondrocyte matrix degradation was examined by western blotting. Further, the effect of integrin α2ß1 inhibitor on T-2 toxin-induced chondrocyte apoptosis was analyzed. About 100 ng/g body weight (BW)/day T-2 toxin was fed to Sprague-Dawley (SD) rats, T-2 toxin treatment (0, 6, 12, and 24 ng/mL) induced C28/I2 chondrocytes. Both in vivo and in vitro, chondrocyte survival was inhibited, and the production of type II collagen was significantly reduced (p < 0.05). However, the level of MMP-13 was up-regulated (p < 0.05). Matrix degradation was effectively blocked after the pre-treatment by integrin α2ß1 inhibitor (p < 0.05). Conclusively, Integrin α2ß1 is a critical signaling pathway for communication between cells and the extracellular matrix, the present study provides a new clue to elucidate the mechanism of T-2 toxin-induced chondrocyte damage.


Assuntos
Colágeno Tipo II/metabolismo , Integrina alfa2beta1/metabolismo , Toxina T-2/toxicidade , Animais , Cartilagem Articular , Colágeno , Humanos , Metaloproteinase 13 da Matriz , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
9.
Lung Cancer ; 145: 1-9, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32387812

RESUMO

OBJECTIVES: Osimertinib is active against epidermal growth factor receptor (EGFR) T790M-mutated non-small cell lung cancer (NSCLC). However, its efficacy against complex EGFR mutations with T790M has not been evaluated. MATERIALS AND METHODS: In order to detect complex EGFR mutations, we consecutively sequenced cancer tissues by RNA reverse transcription polymerase chain reaction. Patients with advanced NSCLC with activating EGFR mutation and secondary T790M who received osimertinib were enrolled. Patients' clinicopathologic characteristics, prior treatment details, and osimertinib treatment outcomes were analyzed. RESULTS: Totally, 165 sequenced patients were analyzed. Eleven (7%) of them had complex EGFR mutations with T790M. The osimertinib response rate was 27%. They had a shorter progression-free survival (PFS) (median, 2.9 and 9.7 months, p < 0.001) and overall survival (OS) (median, 17.8 and 31.0 months, p = 0.01) than patients with a single EGFR mutation with T790M. After osimertinib failure, seven patients received rebiopsy with molecular analysis. Four lost the T790M, two transformed to small cell and one acquired C797S. Moreover, taking the median as the demarcation, patients received shorter prior EGFR tyrosine kinase inhibitor (TKI) treatment duration had a shorter osimertinib PFS (median, 7.3 and 13.8 months, p < 0.001) and OS (median, 21.5 and 36.7 months, p = 0.003). Multivariate Cox regression analysis confirmed complex EGFR mutations and prior EGFR TKI treatment duration were independent factors for osimertinib PFS and OS. CONCLUSIONS: Complex EGFR mutations and shorter prior EGFR TKI treatment duration may confer shorter osimertinib PFS and OS in advanced NSCLC with secondary T790M mutation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico
10.
Oncologist ; 25(8): 702-711, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32386255

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression is associated with clinical outcomes of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (ADC) treated with tyrosine kinase inhibitors (TKIs). However, whether PD-L1 expression plays a role in anaplastic lymphoma kinase (ALK)-positive lung ADC is unknown. We aimed to evaluate the impact of PD-L1 in patients with ALK-positive lung ADC receiving crizotinib. MATERIALS AND METHODS: PD-L1 expression was identified by immunohistochemistry (IHC). Reverse transcriptase-polymerase chain reaction was used for ALK variant detection, and immunofluorescence-based multiplex staining was applied for exploring immune cells in tumor microenvironments. RESULTS: A total of 78 patients with ALK-positive advanced ADC were enrolled in our study, of whom 52 received crizotinib. Compared with EGFR/ALK wild-type tumors, PD-L1 expression was lower in ALK-positive ADC. ALK fusion variants were identified in 32 patients, and those with variant 3 and 5 (short variants) had higher PD-L1 expression than those with other variants. The crizotinib objective response rate (ORR) and progression-free survival (PFS) was better in tumors with negative PD-L1 expression (ORR/PFS in PD-L1 0% vs. 1%-49% vs. 50%-100%: 60.7%/11.8 months vs. 38.5%/6.5 months vs. 36.4%/4.0 months, p = .007/.022). The multivariate Cox proportional hazards model revealed that PD-L1 0% (vs. ≥1%) was an independent factor for longer PFS (adjusted hazard ratio 0.322, 95% confidence interval 0.160-0.650, p = .002). Multiplex IHC in three cases showed a varied extent of immune cell infiltrations in tumors with different PD-L1 expression. CONCLUSION: Positive PD-L1 expression was associated with unfavorable clinical outcomes in patients with ALK-positive lung ADC receiving crizotinib. IMPLICATIONS FOR PRACTICE: Not all lung adenocarcinoma with sensitizing driver mutations experienced durable responses to small-molecule tyrosine kinase inhibitors (TKIs). Similar to the negative impact of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor mutant tumors treated with TKIs, this study demonstrated that positive PD-L1 expression was also associated with worse response rate and shorter progression-free survival of anaplastic lymphoma kinase (ALK)-positive adenocarcinoma treated with crizotinib. Among different ALK fusion partners, tumors with short variants (V3 and V5) had higher PD-L1 compared with long variants (V1, V2, and V6). Testing PD-L1 before initiating crizotinib for ALK-positive lung cancer could be a simple method to provide important prognostic information.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Antígeno B7-H1/genética , Crizotinibe/farmacologia , Crizotinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Microambiente Tumoral
11.
Cancer Biomark ; 28(3): 351-363, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32417760

RESUMO

BACKGROUND: EGFR-mutant lung cancer inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). OBJECTIVE: To investigate the clinical relevance of microRNAs (miRNAs) in TKI therapy response and resistance. METHODS: We performed a miRNA PCR array analysis and used The Cancer Genome Atlas (TCGA) database to identify potential miRNAs related to EGFR TKIs resistance. We then correlated miRNA expression in 70 surgical and 50 malignant pleural effusion specimens with patient outcomes in those with non-small cell lung carcinoma. Molecular manipulation was performed in EGFR mutant lung cancer cells to assess the effect of miR-200c-3p on cell migratory ability and EGFR-TKI sensitivity. RESULTS: We identified miR-200c-3p and miR-203a-3p as potential EGFR TKI resistance regulators via their modulation of epithelial-to-mesenchymal transition (EMT). MiR-200c-3p and miR-203a-3p were down-regulated in EGFR TKI-resistant cell lines. Progression-free survival (PFS) with EGFR-TKI treatment of patients with high miR-200c-3p expression, but not miR-203a-3p, in the specimens was significantly longer than that of patients with low expression. MiR-200c-3p overexpression inhibited the EMT process in EGFR TKI resistance cell lines and promoted cell death. MiR-200c-3p silencing in EGFR TKI sensitive cell lines increased drug resistance. CONCLUSION: MiR-200c-3p plays a role in sensitivity to EGFR TKIs via modulating EMT process.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/terapia , MicroRNAs/metabolismo , Derrame Pleural Maligno/terapia , Inibidores de Proteínas Quinases/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Estimativa de Kaplan-Meier , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Mutação , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/mortalidade , Derrame Pleural Maligno/patologia , Pneumonectomia , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico
12.
Anal Chem ; 92(1): 1309-1315, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31820634

RESUMO

The ability to rapidly and accurately detect water toxicity is crucial for monitoring water quality and assessing toxic risk, but such detection remains a great challenge. Here, we present a plasmonic nanomechanical sensing (PNMS) system for the rapid assessment of water toxicity. This technique is based on the plasmonic sensing of the nanomechanical movement of single bacterial cells, which could be inhibited upon exposure to potential toxicants. By correlating the amplitude of nanomechanical movement with bacterial activity, we detected a variety of toxic substances in water. The direct readout of bacterial activity via PNMS allowed for a high sensitivity to toxicants in water, thereby enabling us to evaluate the acute toxicological effect of chemical compounds rapidly. The PNMS method is promising for online alerts of water quality safety and for assessing chemical hazards. We anticipate that PNMS is also suitable for a wide range of other applications, including bacterial detection and high-throughput screening of antibacterial materials.


Assuntos
Antibacterianos/análise , Bacillus thuringiensis/química , Escherichia coli/química , Substâncias Perigosas/análise , Sistemas Microeletromecânicos , Poluentes Químicos da Água/análise , Bacillus thuringiensis/citologia , Bacillus thuringiensis/crescimento & desenvolvimento , Cobre/análise , Monitoramento Ambiental , Escherichia coli/citologia , Escherichia coli/crescimento & desenvolvimento , Fenóis/análise , Qualidade da Água
13.
Front Oncol ; 9: 880, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31608224

RESUMO

Patients' clinical factors and genetics factors such as anaplastic lymphoma kinase (ALK) fusion variants and BIM (Bcl-2-like 11) polymorphism were reported to be associated with clinical outcome in crizotinib-treated advanced non-small cell lung cancer (NSCLC). However, the results were still controversial. We analyzed outcome of 54 patients with known ALK fusion variants who received crizotinib for advanced NSCLC. Thirty of them had successful BIM polymorphism analysis and 6 (20%) had a BIM deletion. Multivariate Cox regression analysis found that previous anticancer therapy [adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI), 1.04-1.76 for each additional line of therapy, p = 0.025] and Eastern Cooperative Oncology Group (ECOG) performance status ≥2 (aHR 8.35, 95% CI, 1.52-45.94, p = 0.015) were independent factors for progression-free survival (PFS). Only ECOG performance status ≥2 (aHR 7.20, 95% CI, 1.27-40.79, p = 0.026) was an independent factor for overall survival (OS). Neither ALK fusion variants nor the presence of a BIM deletion was associated with crizotinib PFS or OS. After adjusting with clinical factors, different ALK variants and BIM polymorphism might not be independent factors for crizotinib PFS or OS in advanced NSCLC with ALK rearrangement.

14.
Int J Cancer ; 145(6): 1609-1624, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31162839

RESUMO

Constitutive activation of the epidermal growth factor receptor (EGFR) signaling pathway is implicated in the initiation and progression of lung cancer. EGFR tyrosine kinase inhibitor (TKI)-targeted therapy has become the standard treatment for nonsmall cell lung cancer (NSCLC) patients. However, acquired resistance to these agents remains a major obstacle for managing NSCLC. Here, we investigated a novel strategy to overcome EGFR TKI resistance by targeting the stanniocalcin 2 (STC2)-JUN-AXL pathway. We revealed that STC2 was expressed at significantly higher levels in EGFR TKI-resistant cells. Further, clinical analysis showed that STC2 expression was increased after the development of EGFR TKI resistance and that higher levels were correlated with shorter progression-free survival in EGFR TKI-treated lung cancer patients. Moreover, STC2 overexpression in EGFR TKI-sensitive cells resulted in EGFR TKI resistance. Conversely, genetic silencing of STC2 rendered EGFR TKI-resistant cells more sensitive to EGFR TKIs. Mechanically, STC2 enhanced AXL promoter activity by increasing the phosphorylation of c-Jun, which is an indispensable transcription factor that transactivates AXL. STC2 promoted activation of the JUN-AXL-extracellular signal-regulated kinase (ERK) signaling axis in lung cancer cells. Pharmacological or genetic inhibition of AXL-ERK activity inhibited STC2-mediated EGFR TKI resistance. We also demonstrated that PE2988 cells, a C797S-independent osimertinib-resistant primary cancer cell line from a lung cancer patient, responded to combined AXL inhibitor and osimertinib treatment. In conclusion, our research indicates that STC2 overexpression is important for acquired resistance to EGFR TKIs and that STC2-JUN-AXL-ERK signaling might be a potential therapeutic target to overcome resistance to EGFR TKIs.


Assuntos
Adenocarcinoma/metabolismo , Inibidores Enzimáticos/farmacologia , Glicoproteínas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/antagonistas & inibidores , Xenoenxertos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação
15.
Cancers (Basel) ; 11(6)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234388

RESUMO

BRAF V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC). The usefulness of immunohistochemistry (IHC) as an alternative diagnostic tool has not been validated. Moreover, the clinical information of patients with BRAF V600E-mutated lung ADC is limited. We retrospectively identified 31 lung ADCs diagnosed with BRAF V600E mutation by standard molecular sequencing methods and reviewed their clinical characteristics and pathological features. An anti-BRAF V600E monoclonal VE1 antibody for IHC was used to confirm the expression patterns. The series was comprised of 99 cases, 29 with BRAF V600E mutation and 70 without BRAF V600E but with other types or undetected mutations. The majority of BRAF V600E-mutated biopsied tissues were poorly differentiated and micropapillary patterns. Application of the IHC VE1 assay was highly feasible in primary/metastatic sites or effusion blocks, yielding positive findings in 28 of 29 (96.6%) BRAF V600E-mutated tumors and negative results in 69 of 70 (98.6%) tumors harboring other types or undetected mutations. Patients who received pemetrexed/platinum-based rather than mutation-targeted chemotherapy as the first-line therapy for metastatic disease showed median overall survival of 15.5 months. Our findings indicated that VE1 antibody-based IHC analysis demonstrated high sensitivity and specificity to detect BRAF V600E-mutated lung ADCs in tissues from primary or metastatic sites.

16.
Cancers (Basel) ; 11(2)2019 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-30813457

RESUMO

Tumor metastasis is a hallmark of cancer, with distant metastasis frequently developing in lung cancer, even at initial diagnosis, resulting in poor prognosis and high mortality. However, available biomarkers cannot reliably predict cancer spreading sites. The metastatic cascade involves highly complicated processes including invasion, migration, angiogenesis, and epithelial-to-mesenchymal transition that are tightly controlled by various genetic expression modalities along with interaction between cancer cells and the extracellular matrix. In particular, microRNAs (miRNAs), a group of small non-coding RNAs, can influence the transcriptional and post-transcriptional processes, with dysregulation of miRNA expression contributing to the regulation of cancer metastasis. Nevertheless, although miRNA-targeted therapy is widely studied in vitro and in vivo, this strategy currently affords limited feasibility and a few miRNA-targeted therapies for lung cancer have entered into clinical trials to date. Advances in understanding the molecular mechanism of metastasis will thus provide additional potential targets for lung cancer treatment. This review discusses the current research related to the role of miRNAs in lung cancer invasion and metastasis, with a particular focus on the different metastatic lesions and potential miRNA-targeted treatments for lung cancer with the expectation that further exploration of miRNA-targeted therapy may establish a new spectrum of lung cancer treatments.

17.
World J Clin Cases ; 7(5): 676-683, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30863769

RESUMO

BACKGROUND: Cystic adenomyosis is a special type of adenomyosis. Its clinical manifestations lack specificity. Pelvic ultrasound and nuclear magnetic resonance imaging can help clarify the diagnosis. Because cystic uterine adenomyosis is rare in clinical work, it can be easily misdiagnosed or its diagnosis can be missed. Early surgical treatment and postoperative drug treatment can alleviate dysmenorrhea, menorrhagia, anemia, and other symptoms. CASE SUMMARY: Two cases complained about abnormal vaginal bleeding and were diagnosed with intrauterine cystic adenomyosis by gynecological ultrasound and pathological examination. The clinical manifestations included dysmenorrhea, hypermenorrhea, and a history of cesarean section. Both cases underwent a surgery, and chocolate-like liquid was released from the cystic mass in the uterus and the manifestations were relieved. CONCLUSION: Intrauterine cystic adenomyosis could be diagnosed by pathological examination and treated by hysterectomy or hystscopy to release the liquid inside.

18.
CNS Neurosci Ther ; 25(6): 759-771, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30720246

RESUMO

AIMS: Vanishing white matter disease (VWM) is an inherited leukoencephalopathy in children attributed to mutations in EIF2B1-5, encoding five subunits of eukaryotic translation initiation factor 2B (eIF2B). Although the defects are in the housekeeping genes, glial cells are selectively involved in VWM. Several studies have suggested that astrocytes are central in the pathogenesis of VWM. However, the exact pathomechanism remains unknown, and no model for VWM induced pluripotent stem cells (iPSCs) has been established. METHODS: Fibroblasts from two VWM children were reprogrammed into iPSCs by using a virus-free nonintegrating episomal vector system. Control and VWM iPSCs were sequentially differentiated into neural stem cells (NSCs) and then into neural cells, including neurons, oligodendrocytes (OLs), and astrocytes. RESULTS: Vanishing white matter disease iPSC-derived NSCs can normally differentiate into neurons, oligodendrocytes precursor cells (OPCs), and oligodendrocytes in vitro. By contrast, VWM astrocytes were dysmorphic and characterized by shorter processes. Moreover, δ-GFAP and αB-Crystalline were significantly increased in addition to increased early and total apoptosis. CONCLUSION: The results provided further evidence supporting the central role of astrocytic dysfunction. The establishment of VWM-specific iPSC models provides a platform for exploring the pathogenesis of VWM and future drug screening.


Assuntos
Astrócitos/fisiologia , Leucoencefalopatias/fisiopatologia , Adolescente , Criança , Feminino , Fibroblastos/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Masculino , Células-Tronco Neurais/fisiologia
19.
Cancers (Basel) ; 11(1)2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30609749

RESUMO

Patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer show a dramatic response to EGFR-tyrosine kinase inhibitors (TKIs). However, acquired drug resistance eventually develops. This study explored the novel mechanisms related to TKI resistance. To identify the genes associated with TKI resistance, an integrative approach was used to analyze public datasets. Molecular manipulations were performed to investigate the roles of insulin-like growth factor binding protein 7 (IGFBP7) in lung adenocarcinoma. Clinical specimens were collected to validate the impact of IGFBP7 on the efficacy of EGFR TKI treatment. IGFBP7 mRNA expression in cancer cells isolated from malignant pleural effusions after acquired resistance to EGFR-TKI was significantly higher than in cancer cells from treatment-naïve effusions. IGFBP7 expression was markedly increased in cells with long-term TKI-induced resistance compared to in TKI-sensitive parental cells. Reduced IGFBP7 in TKI-resistant cells reversed the resistance to EGFR-TKIs and increased EGFR-TKI-induced apoptosis by up-regulating B-cell lymphoma 2 interacting mediator of cell death (BIM) and activating caspases. Suppression of IGFBP7 attenuated the phosphorylation of insulin-like growth factor 1 receptor (IGF-IR) and downstream protein kinase B (AKT) in TKI-resistant cells. Clinically, higher serum IGFBP7 levels and tumors with positive IGFBP7-immunohistochemical staining were associated with poor TKI-treatment outcomes. IGFBP7 confers resistance to EGFR-TKIs and is a potential therapeutic target for treating EGFR-TKI-resistant cancers.

20.
Environ Pollut ; 243(Pt A): 462-471, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30216878

RESUMO

Microplastics (MPs) have the potential to interact with the toxicity of other common environmental contaminants, such as heavy metals. Here, we investigated the impacts of polystyrene-MPs (32-40 µm), cadmium (Cd) and their combination on early juveniles of the discus fish (Symphysodon aequifasciatus) in relation to Cd accumulation, antioxidant defence and innate immunity. Animals were exposed to three concentrations of MPs (0, 50 or 500 µg L-1) crossed with two levels of Cd (0 or 50 µg L-1) for 30 days. Our findings showed that MPs and Cd had no adverse effects on growth and survival. Under exposure to Cd, however, accumulation of Cd in the body of fish decreased with increasing MP concentrations as supported by a reduced metallothionein content. The activities of superoxide dismutase and glutathione peroxidase increased with MPs but decreased with Cd. MPs, Cd or the mixture increased catalase activity, despite an antagonistic interaction between the two stressors. Glutathione levels increased when exposed to high MP concentrations but decreased when co-exposed to Cd. Malondialdehyde content was only influenced by MPs and increased with elevated MPs. MPs or Cd alone did not increase protein carboxyl content but showed a synergistic effect and increased content. MPs or Cd alone showed no effect on lysozyme activity but had a synergistic effect and activated activity. Activities of both acid phosphatase and alkaline phosphatase were enhanced by MPs, Cd or their mixture, although there was an antagonistic interaction between the two stressors. In contrast, MPs, Cd or their mixture decreased complement 3 content, despite an antagonistic interaction between the two stressors. Collectively, this study suggests that exposure to Cd led to reduced Cd accumulation in the presence of MPs. Nevertheless, co-exposure could induce severe oxidative stress and stimulate innate immunity in the juvenile S. aequifasciatus.


Assuntos
Antioxidantes/metabolismo , Cádmio/metabolismo , Cádmio/toxicidade , Ciclídeos/imunologia , Ciclídeos/metabolismo , Imunidade Inata/efeitos dos fármacos , Plásticos/toxicidade , Animais , Catalase/metabolismo , Ciclídeos/crescimento & desenvolvimento , Complemento C3/metabolismo , Gastrópodes , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Metalotioneína/metabolismo , Metais Pesados/toxicidade , Muramidase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Monoéster Fosfórico Hidrolases/metabolismo , Superóxido Dismutase/metabolismo , Análise de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...