Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
1.
Opt Lett ; 49(7): 1741-1744, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38560851

RESUMO

Speckle-correlation optical scattering imaging (SCOSI) has shown the potential for non-invasive biomedical diagnostic applications, which directly utilizes the scattering patterns to reconstruct the deep and non-line-of-sight objects. However, the course of the translation of this technique to preclinical biomedical imaging applications has been postponed by the following two facts: 1) the field of view of SCOSI was significantly limited by the optical memory effect, and 2) the molecular-tagged functional imaging of the biological tissues remains largely unexplored. In this work, a proof-of-concept design of the first-generation widefield functional SCOSI (WF-SCOSI) system was presented for simultaneously achieving mesoscopic mapping of fluid morphology and flow rate, which was realized by implementing the concepts of scanning synthesis and fluorescence scattering flowmetry. The ex vivo imaging results of the fluorescence-labeled large-scale blood vessel network phantom underneath the strong scatters demonstrated the effectiveness of WF-SCOSI toward non-invasive hemodynamic imaging applications.


Assuntos
Diagnóstico por Imagem , Hemodinâmica , Imagens de Fantasmas , Reologia , Desenho de Equipamento , Imagem Óptica/métodos
2.
World J Gastrointest Oncol ; 16(1): 110-117, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38292839

RESUMO

BACKGROUND: The incidence of gastric cancer remains high, and it is the sixth most common cancer and the fourth leading cause of cancer deaths worldwide. Oral contrast-enhanced ultrasonography is a simple, non-invasive, and painless method for the diagnosis of gastric tumors. AIM: To explore the diagnostic value of oral contrast-enhanced ultrasonography for the detection of gastric tumors. METHODS: The screening results based on oral contrast-enhanced ultrasonography and electronic gastroscopy were compared with those of the postoperative pathological examination. RESULTS: Among 42 patients with gastric tumors enrolled in the study, the diagnostic accordance rate was 95.2% for oral contrast-enhanced ultrasonography (n = 40) and 90.5% for electronic gastroscopy (n = 38) compared with postoperative pathological examination. The Kappa value of consistency test with pathological findings was 0.812 for oral contrast-enhanced ultrasonography and 0.718 for electronic gastroscopy, and there was no significant difference between them (P = 0.397). For the TNM staging of gastric tumors, the accuracy rate of oral contrast-enhanced ultrasonography was 81.9% for the overall T staging and 50%, 77.8%, 100%, and 100% for T1, T2, T3, and T4 staging, respectively. The sensitivity and specificity were both 100% for stages T3 and T4. The diagnostic accuracy rate of oral contrast-enhanced ultrasonography was 93.8%, 80%, 100%, and 100% for stages N0, N1-N3, M0, and M1, respectively. CONCLUSION: The accordance rate of qualitative diagnosis by oral contrast-enhanced ultrasonography is comparable to that of gastroscopy, and it could be used as the preferred method for the early screening of gastric tumors.

3.
Adv Mater ; 35(16): e2209768, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36738144

RESUMO

Molecular solar thermal (MOST) materials, which can efficiently capture solar energy and release it as heat on demand, are promising candidates for future personal thermal management (PTM) applications, preferably in the form of fabrics. However, developing MOST fabrics with high energy-storage capacity and stable working performance remains a significant challenge because of the low energy density of the molecular materials and their leakage from the fabric. Here, an efficient and robust MOST fabric for PTM using azopyrazole-containing microcapsules with a deep-UV-filter shell is reported. The MOST fabric, which can co-harvest solar and thermal energy, achieves efficient photocharging and photo-discharging (>90% photoconversion), a high energy density of 2.5 kJ m-2 , and long-term storage sustainability at month scale. Moreover, it can undergo multiple cycles of washing, rubbing, and recharging without significant loss of energy-storage capacity. This MOST microcapsule strategy is easily used for the scalable production of a MOST fabric for solar thermal moxibustion. This achievement offers a promising route for the application of wearable MOST materials with high energy-storage performance and robustness in PTM.

4.
ACS Appl Mater Interfaces ; 15(3): 4623-4634, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36644925

RESUMO

Mechanoluminescent (ML) materials can emit visible light by utilizing mechanical energy, which shows unique advantages in visual mechanical sensing, displays, and biomechanical monitoring due to the correlation between force stimulation and luminescence intensity. Most organic ML materials exhibit luminescence intensity attenuation, disappearing completely with force stimulation and failing to recover. Here, organic luminogens (Cz-alkyl6) can be synthesized by introducing a soft alkyl chain into the carbazole, which exhibits ML emission with self-assembly units. Furthermore, organic luminogens can be generated repeatedly by simply recrystallizing the fracture crystal in situ after a short thermal treatment (70 °C) within 14 s. More importantly, the quantitative correlation between force pressure and ML intensity has been established by a sandwich-type ML device based on a novel carbazole derivative (Cz-alkyl6). The ML device presents a capacity for detecting mechanical signals up to 13 N according to its ML intensity (≤275 a.u.), exhibiting potential application value in engineering damage detection, anticounterfeiting, and advanced visual mechanical sensing.

5.
Angew Chem Int Ed Engl ; 61(44): e202212483, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36102669

RESUMO

Leuco dye-based thermochromic materials offer enormous potential for visible molecular logic due to the appealing reversible color-changing effect. The stable color state is uncontrollable as it depends only on the spontaneous protonation of the leuco dye and color developer. There is still a challenge to propose an effective approach to control bistable color function at required temperature. A family of azobenzenes with various alkyl chains (AZO(n)) is designed for protonation competition with leuco dye. The hydrogen bond and Van der Waals forces are formed between color developer and AZO(n). The color developer can be locked to provide the proton for the leuco dye by Z-AZO(n), while it can be released upon Z-to-E photoisomerization. The locked state can be lasted for more than 16 hours. This optically controlled leuco dye-based system demonstrates a visible sequential logic operation with four-input signals, and provides a new type of protonation-based optical control.

6.
Lab Invest ; 101(9): 1130-1141, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34006890

RESUMO

The PHLDA3 gene encodes a small 127 amino acid protein with a pleckstrin homology (PH)-only domain. The expression and significance of PHLDA3 in lung cancer remain unclear. Here, we investigated the role of PHLDA3 in tumor proliferation and invasion in lung adenocarcinoma. Immunohistochemistry and immunoblotting analyses were used to assess PHLDA3 expression in lung cancer tissues, and its correlation with clinicopathological factors in lung cancer. Plasmids encoding PHLDA3 and small interfering RNA against PHLDA3 were used to regulate the expression of PHLDA3 in lung cancer cells. Furthermore, the effects of PHLDA3 on lung cancer cell proliferation and invasion were investigated using the MTS, colony formation, Matrigel invasion, and wound healing assays. Co-immunoprecipitation analysis and inhibitors of both the Wnt signaling pathway and GSK3ß were used to explore the regulatory mechanisms underlying the role of PHLDA3 in lung cancer cells. PHLDA3 was found to be overexpressed in lung cancer tissues, and its expression was correlated with poor outcomes in lung adenocarcinoma patients. PHLDA3 expression promoted the proliferation, invasion, and migration of lung cancer cells. Overexpression of PHLDA3 activated the Wnt signaling pathway and facilitated epithelial-mesenchymal transition. Inhibition of Wnt signaling pathway activity, using XAV-939, reversed the effects of PHLDA3 overexpression in lung cancer cells; moreover, PHLDA3 could bind to GSK3ß. Inhibition of GSK3ß activity, using CHIR-99021, restored the proliferative and invasive abilities of PHLDA3 knockdown cells. Our findings demonstrate that PHLDA3 is highly expressed in lung adenocarcinomas and is correlated with poor outcomes. Furthermore, it promotes the proliferation and invasion of lung cancer cells by activating the Wnt signaling pathway.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas Nucleares , Via de Sinalização Wnt/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo
7.
Ying Yong Sheng Tai Xue Bao ; 32(3): 967-975, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754563

RESUMO

Taking 7-year-old apple trees (Hanfu) as the test material, an experiment with three irrigation levels including high water (W1, 85%-100%θf, θf was the field water holding capacity), medium water (W2, 70%-85%θf) and low water (W3, 55%-70%θf), and three nitrogen application levels, high (N1, 600 kg·hm-2), medium (N2, 400 kg·hm-2) and low (N3, 200 kg·hm-2), was conducted to investigate the effects of water and nitrogen coupling on photosynthetic characteristics, yield and water and nitrogen utilization of apple trees in mountainous areas under surge-root irrigation (SRI). The results showed that the net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (gs), intercellular CO2 concentration (Ci), leaf instantaneous water use efficiency (WUEi) of apple trees leaves decreased with decreasing nitrogen application rates under the same irrigation amount, but Ci increased. Under the same nitrogen application rate, foliar Pn, Tr, gs and WUEi decreased with decreasing irrigation amount, but Ci increased. The daily average values of Pn and Tr under W1N1 treatment were the largest, while W2N2 treatment had the largest WUEi. Apple yield, irrigation water use efficiency (IWUE) and nitrogen partial productivity (NPFP) were significantly affected by irrigation and nitrogen application. The W2N2 treatment had the highest yield (26761 kg·hm-2). IWUE increased significantly with the decreasing irrigation and the increasing nitrogen application, while NPFP increased significantly with the increases of irrigation and the decreases of nitrogen application. Results of the regression analysis showed that the combination of irrigation and nitrogen application was closest to W2N2 treatment when yield and IWUE got the optimal solution. Therefore, W2N2 treatment was the best combination mode of water and nitrogen application for apple under SRI in Northern Shaanxi mountain area.


Assuntos
Malus , Nitrogênio , Irrigação Agrícola , Biomassa , China , Fertilizantes , Água
8.
J Mol Histol ; 52(1): 11-20, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33128167

RESUMO

Thyroid hormone receptor interactor 13 (TRIP13) is an ATPase that has been found to be overexpressed in many tumors. The aim of this study was to investigate the role of TRIP13 and its mechanism of action in lung cancer. The expression of TRIP13 was examined in lung cancer tissues and corresponding normal lung tissues by western blotting. TRIP13 was overexpressed or knocked down by transient transfection or siRNA interference in lung cancer cells, respectively. The expression of key proteins associated with the Wnt signaling pathway and epithelial-mesenchymal transition (EMT) was assessed. The interaction between TRIP13 and low-density lipoprotein receptor-related protein 6 (LRP6) was examined by co-immunoprecipitation and laser confocal immunofluorescence. Moreover, this study determined the proliferative and invasive ability of cells through colony formation, cell proliferation, and Matrigel invasion assays. The expression of TRIP13 was higher in lung cancer tissues than in normal lung tissues (p = 0.002), and this correlated with poor patient prognosis (p < 0.001). In addition, overexpression of TRIP13 enhanced the levels of active ß-catenin and target proteins of the Wnt signaling pathways (p < 0.05). This study found that TRIP13 can co-localize and bind with LRP6. Furthermore, overexpression of TRIP13 caused the upregulation of N-cadherin, Snail, and vimentin, and the downregulation of E-cadherin (p < 0.05). The aforementioned results were reversed after knocking down the expression of TRIP13 (p < 0.05). TRIP13 is highly expressed in lung cancers, indicating poor prognosis. overexpression of TRIP13 promotes the proliferative and invasive ability of lung cancer cells via the activation of Wnt signaling pathway and EMT.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas de Ciclo Celular/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Via de Sinalização Wnt , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Invasividade Neoplásica , Estadiamento de Neoplasias , Análise de Sobrevida , Ensaio Tumoral de Célula-Tronco
9.
Appl Microbiol Biotechnol ; 104(21): 9159-9177, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32970179

RESUMO

Huperzine A (Hup A) is an important drug for treating Alzheimer's disease (AD) and mainly extracted from the Huperzia serrata (Thunb.) Trevis. (Lycopodiaceae) (HS). Nevertheless, the content of Hup A in HS is very low of 0.007% with growing circle of 8 to 10 years, and the chemical synthesis of Hup A still has some insurmountable limitations in the industrialized production. So, the available resources of Hup A for clinical treatment of AD are scarce. The purpose of this work was to construct a biosynthesis platform based on the endophytic fungi from HS. In this work, five endophytic fungi Mucor racemosus NSH-D, Mucor fragilis NSY-1, Fusarium verticillioides NSH-5, Fusarium oxysporum NSG-1, and Trichoderma harzianum NSW-V were firstly found and isolated from the Chinese folk medicine HS, which were identified according to their morphological characteristics and nuclear ribosomal DNA ITS sequences. The highest efficient fungus could effectively biosynthesize Hup A in a liquid culture of 319.8 ± 0.17 mg/L which were 112 times higher than that of other reported conventional endophytic fungi. Moreover, these fungi with higher hereditary stability could possess the initial expressing ability of Hup A after 40 generations, and the expressed Hup A from these biosynthesis systems has prior physicochemical properties, a better inhibition activity of acetylcholinesterase and a lower cytotoxicity compared with the listed active pharmaceutical ingredients (APIs) of Hup A. These results provide promising alternative resources for producing Hup A at an industrial scale by biosynthesis, and it may also shed light on millions of AD patients. KEY POINTS: • Five novel endophytic fungi with high stability could highly express prior Hup A Graphical abstract.


Assuntos
Doença de Alzheimer , Huperzia , Sesquiterpenos , Alcaloides , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase , Endófitos , Fusarium , Humanos , Hypocreales , Mucor
10.
Eur J Pharm Sci ; 153: 105496, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32736094

RESUMO

In this work, a novel embolic microspheres with micro nano binary progressive structure (MN-Ms) were developed for transarterial chemoembolization (TCE) applications. The Bletilla striata polysaccharide (Bsp) polymer can inhibit neovascularization and having a dimensional porous network structure, which as the first level of micron structure (microspheres) and will play a role on tumor embolization and inhibition of ischemia-induced neovascularization. The nano flexible liposomes which were embedded by the Bsp polymer microspheres as the second level nano structure to deliver drug across biological membrane barriers. And the micro nano binary progressive structure of MN-Ms was easily formed by using an emulsion crosslinking method. The MN-Ms appeared as perfect round shape with desired swelling and suspensibility characteristics, this was very convenient for embolizing operation by TCE. Due to the binary progressive structure, the MN-Ms could effectively site-specific delivery drug to the targeted liver tissue by enhancing the permeability of Sodium dimethyl-cantharidate (SC) across vessel walls & tissue matrix and delaying drug release at the site of administration, this caused the administrated SC mostly accumulated in the liver, also a higher cytotoxicity to human hepatoma cells. This work indicate that the MN-Ms may be a promising embolic agent for TCE applications for advanced liver cancer.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Liberação Controlada de Fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Microesferas
11.
ACS Appl Mater Interfaces ; 12(19): 21854-21862, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32298571

RESUMO

A sensitive electro-thermochromic Janus fabric driven by voltage is demonstrated via a facial double side coating. The graphene forms a conductive layer that allows Joule heating to supply the thermal resource for the electro-thermochromic behavior of polyester fabric. The thermochromic dye with reversible color-changing property is coated on the opposite side of the graphene layer. The color of electro-thermochromic Janus fabric changes from blue to white with a gradual heating that exceeded 45 °C at the applied voltage of 10 V. The switching rate of color is rapid with the increase of temperature from the room temperature to above 45 °C in 8 s, resulting from the superior resistive heating of the graphene. The electrical conductivity of the electro-thermochromic Janus fabric is not disturbed once undergoing a bending angle range from 30° to 150° and the temperature remains stable after 1000 bending cycles which clearly indicates the excellent flexibility of the fabric. The steady signal in the heating/cooling curve is observed after 500 cycles, pointing out the outstanding durability of the electro-thermochromic Janus fabric under the supplied voltage. It is realizable that the color of electro-thermochromic Janus fabric is triggered accurately by varying the supplied voltage. The simplicity of this design makes it attractive for the application of flexible electro-thermochromic textile, such as active visual camouflage, personal thermal management, and information displays.

12.
Front Oncol ; 10: 180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32195172

RESUMO

FAM83A (family with sequence similarity 83, member A) has been found to be highly expressed in cancers. The purpose of this study was to clarify the role and mechanism of FAM83A in lung cancers. The expression of FAM83A in lung cancer cells was enhanced by gene transfection or knocked down by small interfering RNA interference. The key proteins of the Wnt signaling pathway, the Hippo signaling pathway, and epithelial-mesenchymal transition (EMT) were examined using Western blot. The proliferation and invasion of lung cancer cells were examined using cell proliferation, colony formation, and invasion assays. The expression of FAM83A in lung cancer tissues was significantly increased and was correlated with advanced tumor-node-metastasis (TNM) stage and poor prognosis. Overexpression of FAM83A enhanced the proliferation, colony formation, and invasion of lung cancer cells. Meanwhile, FAM83A overexpression increased the expression of active ß-catenin and Wnt target genes and the activity of EMT. Furthermore, in FAM83A-overexpressed cells, the activity of Hippo pathway was downregulated, whereas the expression of yes-associated protein (YAP) and its downstream targets cyclin E and CTGF were upregulated. The inhibitor of the Wnt signaling pathway, XAV-939, reversed the promoting effect of FAM83A on YAP, cyclin E, and CTGF. On knocking down the expression of FAM83A, we obtained the opposite results. However, the inhibitor of GSK3ß, CHIR-99021, restored the expression of YAP, cyclin E, and CTGF after FAM83A was knocked down. FAM83A is highly expressed in lung cancers and correlated with advanced TNM stage and poor prognosis. FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process.

14.
Gut ; 69(7): 1239-1247, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31744910

RESUMO

OBJECTIVE: Dietary fibre has beneficial effects on energy metabolism, and the majority of studies have focused on short-chain fatty acids produced by gut microbiota. Ginseng has been reported to aid in body weight management, however, its mechanism of action is not yet clear. In this study, we focused on the potential modulating effect of ginseng on gut microbiota, aiming to identify specific strains and their metabolites, especially long-chain fatty acids (LCFA), which mediate the anti-obesity effects of ginseng. DESIGN: Db/db mice were gavaged with ginseng extract (GE) and the effects of GE on gut microbiota were evaluated using 16S rDNA-based high throughput sequencing. To confirm the candidate fatty acids, untargeted metabolomics analyses of the serum and medium samples were performed. RESULTS: We demonstrated that GE can induce Enterococcus faecalis, which can produce an unsaturated LCFA, myristoleic acid (MA). Our results indicate that E. faecalis and its metabolite MA can reduce adiposity by brown adipose tissue (BAT) activation and beige fat formation. In addition, the gene of E. faecalis encoding Acyl-CoA thioesterases (ACOTs) exhibited the biosynthetic potential to synthesise MA, as knockdown (KD) of the ACOT gene by CRISPR-dCas9 significantly reduced MA production. Furthermore, exogenous treatment with KD E. faecalis could not reproduce the beneficial effects of wild type E. faecalis, which work by augmenting the circulating MA levels. CONCLUSIONS: Our results demonstrated that the gut microbiota-LCFA-BAT axis plays an important role in host metabolism, which may provide a strategic advantage for the next generation of anti-obesity drug development.


Assuntos
Tecido Adiposo Marrom/metabolismo , Enterococcus faecalis/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Obesidade/metabolismo , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Panax , Extratos Vegetais/farmacologia , RNA Ribossômico 16S/genética
15.
Soft Matter ; 15(41): 8313-8319, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31565724

RESUMO

The controllability of foam stability is a vital feature that allows for practical applications of foam systems. Light, as an external stimulus, offers unique opportunities to tune the foam stability in a non-invasive manner with high spatiotemporal precision. However, most of the reported photoresposive foams were generated from ionic type surfactants, limiting their applications in industrial complex systems with multiple components. Herein, we design and synthesize a series of nonionic azobenzene surfactants with different polyoxyethylene glycol (EO) chain lengths (BEO-n-Azo, n, referring to the EO chain length, is 14, 19 and 23, respectively) to prepare photoresponsive foams. Detailed insights into the effects of EO chain length on photoisomerization properties, surface tension, as well as foamability and controllable stability of photoresponsive foams are presented. The results demonstrate that photoresposive foams are generated not only from single-component solutions of BEO-n-Azo, but also from multiple-component complex systems doped with BEO-n-Azo, providing a promising strategy to broaden applications of photoresponsive foams in industrial processes.

16.
Cancer Manag Res ; 11: 7485-7497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496806

RESUMO

PURPOSE: Keratin 17 (KRT17) is a 48 KDa type I intermediate filament, which is mainly expressed in epithelial basal cells. KRT17 has been shown to be overexpressed in many malignant tumors and play an important role in the occurrence and development of tumors. Therefore, this study explored the role and underlying mechanism of KRT17 in non-small cell lung cancers (NSCLC). METHODS: KRT17 expression and its correlations with clinicopathological factors were examined in lung cancer tissues by immunohistochemistry. The prognosis value of KRT17 in NSCLCs was retrieved from The Cancer Genome Atlas (TCGA) online databases. The expression level of KRT17 was increased or decreased by KRT17 gene transfection or small RNA interference in lung cancer cells, respectively. Further, proliferation and invasiveness of lung cancer cells were determined by cell proliferation and invasion assays, respectively. Finally, expression levels of proteins related to Wnt signaling pathways and epithelial mesenchymal transition (EMT) were detected by Western blot. RESULTS: The expression level of KRT17 in NSCLCs was significantly higher than normal lung tissues. High expression of KRT17 predicted poor prognosis of patients with NSCLCs, especially lung adenocarcinomas, and was correlated with poor differentiation and lymphatic metastasis. Overexpression of KRT17 enhanced, while KRT17 knockdown inhibited, the proliferation and invasiveness of lung cancer cells. Overexpression of KRT17 up-regulated ß-catenin activity and levels of Wnt target genes, such as cyclin D1, c-Myc, and MMP7. Moreover, KRT17 promoted EMT by up-regulating Vimentin, MMP-9, and Snail expression and down-regulating E-cadherin expression. CONCLUSION: Overexpression of KRT17 is common in NSCLCs and indicates poor prognosis. Overexpression of KRT17 enhances the proliferation and invasiveness of NSCLC cells by activating the Wnt signaling pathway and EMT process. KRT17 is a potential indicator of NSCLC progression and poor survival.

17.
J Exp Clin Cancer Res ; 38(1): 35, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683132

RESUMO

BACKGROUND: The transcription factor PR domain containing 16 (PRDM16) is known to play a significant role in the determination and function of brown and beige fat. However, the role of PRDM16 in tumor biology has not been well addressed. Here we investigated the impact of PRDM16 on tumor growth and metastasis in lung cancer. METHODS: UALCAN database, immunoblotting and immunohistochemistry analysis were used to assess PRDM16 expression in lung cancer patients. Kaplan-Meier plotter database was used to analyze the overall survival of patients with lung cancer stratified by PRDM16 expression. PRDM16 overexpression and knockdown experiments were conducted to assess the effects of PRDM16 on growth and metastasis in vitro and in vivo, and its molecular mechanism was investigated in lung adenocarcinoma cells by chromatin immunoprecipitation-sequencing (ChIP-Seq), real time-quantitative PCR (RT-qPCR), luciferase assay, xenograft models and rescue experiments. RESULTS: PRDM16 was downregulated in lung adenocarcinomas, and its expression level correlated with key pathological characteristics and prognoses of lung adenocarcinoma patients. Overexpressing PRDM16 inhibited the epithelial-to-mesenchymal transition (EMT) of cancer cells both in vivo and in vitro by repressing the transcription of Mucin-4 (MUC4), one of the regulators of EMT in lung adenocarcinomas. Furthermore, deleting the PR domain from PRDM16 increased the transcriptional repression of MUC4 by exhibiting significant differences in histone modifications on its promoter. CONCLUSIONS: Our findings demonstrate a critical interplay between transcriptional and epigenetic modifications during lung adenocarcinoma progression involving EMT of cancer cells and suggest that PRDM16 is a metastasis suppressor and potential therapeutic target for lung adenocarcinomas.


Assuntos
Adenocarcinoma de Pulmão/genética , Proteínas de Ligação a DNA/genética , Mucina-4/genética , Fatores de Transcrição/genética , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Metástase Neoplásica , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Curr Cancer Drug Targets ; 19(8): 674-680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30451112

RESUMO

BACKGROUND: Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinaserelated kinase involved in the pathogenesis of several human cancers. OBJECTIVE: The aim of this study was to investigate the expression and role of NLK in lung cancers, and its underlying mechanisms. METHODS: We examined the expression of NLK in lung cancer tissues through western blot analysis. We enhanced or knocked down NLK expression by gene transfection or RNA interference, respectively, in lung cancer cells, and examined expression alterations of key proteins in the Wnt signaling pathway and in epithelial-mesenchymal transition (EMT). We also examined the roles of NLK in the proliferation and invasiveness of lung cancer cells by cell proliferation, colony formation, and Matrigel invasion assays. RESULTS: NLK expression was found to be significantly higher in lung cancer tissue samples than in corresponding healthy lung tissue samples. Overexpression of NLK correlated with poor prognosis of patients with lung cancer. Overexpression of NLK upregulated ß-catenin, TCF4, and Wnt target genes such as cyclin D1, c-Myc, and MMP7. N-cadherin and TWIST, the key proteins in EMT, were upregulated, while E-cadherin expression was reduced. Additionally, proliferation, colony formation, and invasion turned out to be enhanced in NLK-overexpressing cells. After NLK knockdown in lung cancer cells, we obtained the opposite results. CONCLUSION: NLK is overexpressed in lung cancers and indicates poor prognosis. Overexpression of NLK activates the Wnt signaling pathway and EMT and promotes the proliferation and invasiveness of lung cancer cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Invasividade Neoplásica , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Células Tumorais Cultivadas , Via de Sinalização Wnt
19.
Hum Pathol ; 81: 138-147, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30031101

RESUMO

Malignant peritoneal mesothelioma (MPeM) is an incurable cancer with poor prognosis, and several biomarkers have been suggested for screening of MPeM. The aim of our study was to evaluate the prognostic significances of IMP3 and Fli-1 in MPeM. Diagnostic biopsies of 44 MPeM patients were centrally collected and were immunohistochemically analyzed for expression of IMP3, Fli-1, and Ki-67. Labeling was assessed by 2 pathologists. Complete clinical information and follow-up were obtained from patients' records. Carcinomas expressed Fli-1 in 42 (95.5%) of 44 specimens, and IMP3 in 23 (52.3%) of 44 specimens. Spearman ρ analysis revealed that Fli-1 expression was related to both histologic type and Ki-67 labeling index (Ki-67LI; r = -0.500, P < .05; r = 0.358, P < .05), and IMP3 expression was related to Ki-67LI (r = 0.401, P < .05). A Kaplan-Meier analysis and univariate Cox regression analysis showed that tumor-directed treatment, a lower peritoneal carcinomatosis index, stage I, lower Ki-67LI, and lower level of IMP3 expression had a statistically significantly positive effect on overall survival; Fli-1 did not affect overall survival in the univariate analysis (hazard ratio [HR], 1.026; P = .904). A Kaplan-Meier analysis showed the correlation between IMP3-Fli-1 and overall survival, whereas univariate and multivariate Cox regression analyses did not confirm the correlation. Cox regression analysis revealed that IMP3 expression (HR, 2.311 [95% confidence interval, 1.190-4.486]; P = .013) and no tumor-directed treatment (HR, 0.189 [95% confidence interval, 0.086-0.416]; P = .000) retained independent prognostic significance, both with negative effect on OS. IMP3, along with tumor-directed treatment protocols, is a powerful prognosticator in patients with MPeM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/química , Mesotelioma/química , Neoplasias Peritoneais/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidade , Mesotelioma/patologia , Mesotelioma/terapia , Mesotelioma Maligno , Proteínas dos Microfilamentos/análise , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Proteínas de Ligação a RNA/análise , Receptores Citoplasmáticos e Nucleares/análise , Medição de Risco , Fatores de Risco , Transativadores
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA