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1.
Int J Environ Health Res ; 32(5): 1137-1146, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33164565

RESUMO

The aim of this study was to evaluate the impact of the COVID-19 pandemic on the psychological health and mental health-related lifestyles in Shanghai, China. In the cross-sectional study conducted in May 2020, participants were asked to complete a validated questionnaire including the impact of event scale (IES), social and family support, lifestyle changes, and indicators of negative mental health impact. A total of 430 participants (303 females and 127 males) completed the questionnaire. The overall mean of IES score was 32.3 ± 12.2, indicating a moderate-to-severe mental stress impact. Moreover, there were 68.4% of participant who had IES score ≥26. Females were more likely to get increased support from family and friends, share feeling with them and others, and care for family member's feeling (all P < 0.05). In conclusion, although the COVID-19 pandemic was correlated with high stressful impact, it had associated with some positive mental-health related changes in an urban environment.


Assuntos
COVID-19 , Adulto , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Masculino , Pandemias , SARS-CoV-2 , Estresse Psicológico/epidemiologia , Inquéritos e Questionários
2.
J Sex Med ; 18(11): 1843-1850, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34535368

RESUMO

BACKGROUND: Since January 23, 2020, the Chinese government has imposed restrictive measures including self-isolation, travel restrictions and lockdown of Wuhan city in order to prevent the incoming waves of COVID-19 outbreak in the country. However, the impact of mental health and stress concerns on relationship and sexuality amidst the COVID-19 lockdown was currently unclear. AIM: The cross-sectional study was designed to determine the changes in health, relationship and sexuality among the Chinese couples who lived together amid the early stages of COVID-19 pandemic in China. METHODS: Participants of Chinese nationality aged ≥18 years were asked to complete a self-administered online questionnaire regarding sexuality behaviour and impact of event scale (IES) in March 2020. Nonrandom sampling was used for participant recruitment. Also assessed were sociodemographic data including sex, age, employment, region, sexual dysfunction, and whether participants tested positive for COVID-19. OUTCOMES: IES score, frequency of sexual intercourse per week, quality of usual sex life, emotional bonding and duration of relationship were measured. RESULTS: A total of 1,139 participants (ie, 735 males and 404 females) were included in the study. Mean age and IES of participants was 33.6 ± 9.5 years and 27.4 ± 8.6, respectively. Being male was significantly associated with increased frequency of sexual intercourse amid the COVID-19 pandemic (P = .012). Also, participants with an IES score <26 were more likely to report that they had increased frequency of sexual intercourse per week (P < .001) and the COVID-19 pandemic had positively affected the quality of their usual sex lives (P < .001). On the other hand, participants with IES score ≥26 were more likely to report that the COVID-19 pandemic had positively affected their emotional bonding (P < .001). CLINICAL IMPLICATIONS: Frequency of sexual intercourse and quality of sex life in participants who experienced high stressful impact were more likely to be affected by the COVID-19 pandemic. STRENGTHS AND LIMITATIONS: This was one of the first studies to assess sexual behavior during the COVID-19 pandemic in Chinese adults. Since participants were asked to self-report their sexual behavior, this potentially introduced self-reporting and recall bias into our findings. CONCLUSIONS: Our study reported that despite the moderate-to-severe stressful impact due to the COVID-19 pandemic, the majority reported no significant changes in the frequency of their sexual intercourse per week, quality of their usual sexual lives and emotional bonding. Zhang Y, Wen C, Zhang Y, et al. The Impact of Mental Health and Stress Concerns on Relationship and Sexuality Amidst the COVID-19 Lockdown. J Sex Med 2021;18:1843-1850.


Assuntos
COVID-19 , Saúde Mental , Adolescente , Adulto , Controle de Doenças Transmissíveis , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2 , Comportamento Sexual , Sexualidade
3.
Bone ; 187: 117175, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38917963

RESUMO

While previous studies have demonstrated the role of ubiquitin-conjugating enzyme 2C (UBE2C) in promoting ß-cell proliferation and cancer cell lineage expansion, its specific function and mechanism in bone marrow mesenchymal stem/stromal cells (BMSCs) growth and differentiation remain poorly understood. Our findings indicate that mice with conditional Ube2c deletions in BMSCs and osteoblasts exhibit reduced skeletal bone mass and impaired bone repair. A significant reduction in the proliferative capacity of BMSCs was observed in conditional Ube2c knockout mice, with no effect on apoptosis. Additionally, conditional Ube2c knockout mice exhibited enhanced osteoclastic activity and reduced osteogenic differentiation. Furthermore, human BMSCs with stable UBE2C knockdown exhibited diminished capacity for osteogenic differentiation. Mechanistically, we discovered that UBE2C binds to and stabilizes SMAD1/5 protein expression levels. Interestingly, UBE2C's role in regulating osteogenic differentiation and SMAD1/5 expression levels appears to be independent of its enzymatic activity. Notably, UBE2C regulates osteogenic differentiation through SMAD1/5 signaling. In conclusion, our findings underscore the pivotal role of UBE2C in bone formation, emphasizing its contribution to enhanced osteogenic differentiation through the stabilization of SMAD1/5. These results propose UBE2C as a promising target for BMSC-based bone regeneration.

4.
Biomedicines ; 12(6)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38927412

RESUMO

The periosteum plays a critical role in bone repair and is significantly influenced by the surrounding immune microenvironment. In this study, we employed 10× single-cell RNA sequencing to create a detailed cellular atlas of the swine cranial periosteum, highlighting the cellular dynamics and interactions essential for cranial bone injury repair. We noted that such injuries lead to an increase in M2 macrophages, which are key in modulating the periosteum's immune response and driving the bone regeneration process. These macrophages actively recruit periosteal stromal cells (PSCs) by secreting Neuregulin 1 (NRG1), a crucial factor in initiating bone regeneration. This recruitment process emphasizes the critical role of PSCs in effective bone repair, positioning them as primary targets for therapeutic interventions. Our results indicate that enhancing the interaction between M2 macrophages and PSCs could significantly improve the outcomes of treatments aimed at cranial bone repair and regeneration.

5.
Hepatogastroenterology ; 60(127): 1766-72, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24624456

RESUMO

BACKGROUND/AIMS: Patients of Pancreatic Cancer with B7-H1 over-expression usually have a poor prognosis. In our previous study, the expression of PTEN and B7-H1 were significantly correlated to the carcinogenesis in pancreatic carcinoma. In this study, we investigated the role of the PTEN/mTOR/B7-H1 pathway in immune-resistance, immune escape and progression of pancreatic cancer. METHODOLOGY: siRNAs targeting PTEN were designed, and transfected into pancreatic cancer cell lines. Transwell chamber invasion assay, CCK-8 proliferation assay and siRNA interference assay were used to explore the effect of PTEN on PI3K signaling. Expression of protein and mRNA of the factors involved in PTEN/mTOR/B7-H1 pathway were examined by RT-PCR and Western blot. T Cells apoptosis assay were performed by flow cytometer. RESULTS: Our study demonstrated that B7-H1 was regulated by PTEN through the PI3K/AKT pathway. Loss of PTEN promoted cell proliferation, cell invasion and led to significant increases in the levels of Phospho-AKT, Phospho-mTOR, phospho-S6K1 and B7-H1 proteins. In addition, the increased expression level of B7-H1 when PTEN was knockdown induced T lymphocyte apoptosis. CONCLUSION: Our results demonstrated deletion of PTEN in pancreatic cancer cells induced the expression of B7-H1, which contributed to immune suppression and increased cancer progression and invasion.


Assuntos
Antígeno B7-H1/metabolismo , Proliferação de Células , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias Pancreáticas/enzimologia , Fosfatidilinositol 3-Quinase/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Evasão Tumoral , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Cocultura , Humanos , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Fosforilação , Interferência de RNA , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Fatores de Tempo , Transfecção
6.
Hepatogastroenterology ; 60(121): 176-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22773303

RESUMO

BACKGROUND/AIMS: Pancreaticojejunostomy reconstruction following pancreaticoduodenectomy still remains a debate because of high incidence of complications. To compare the effect of duct-to-mucosa and end-to-side pancreaticojejunostomy reconstruction following pancreaticoduodenectomy, we retrospectively reviewed two groups of patients who underwent duct-to-mucosa or end-to-side pancreaticojejunostomy reconstruction. METHODOLOGY: Over a period of 6 years, 240 consecutive patients underwent duct-to-mucosa (group A) or end-to-side (group B) pancreaticojejunostomy reconstruction following pancreaticoduodenectomy. RESULTS: There were no statistical differences between group A and B in regards to age, gender, preoperative serum levels of total bilirubin, alanine aminotransferase, albumin, pathological features, amount of intraoperative bleeding and duration of operation. The overall incidence of postoperative complications was 26.7 % (22.2% in group A, 30.3% in group B, p>0.05). Of 108 patients in group A, pancreatic fistula occurred in 10 (9.3%) patients and of 132 patients in group B, pancreatic fistula occurred in 14 (10.6%) patients (p>0.05). The overall hospital mortality was 4.2% (3.7% in group A, n=4; 4.5% in group B, n=6, p>0.05). The postoperative hospital stay (mean ±SD) for group A was 20.3±19.7 days, for group B was 23.3+14.3 days (p>0.05). CONCLUSIONS: Our results showed no statistical difference between the two techniques in decreasing postoperative complications including pancreatic fistula or postoperative hospital stay.


Assuntos
Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/métodos , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos
7.
Front Immunol ; 13: 819080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359993

RESUMO

Background: Epigenetic modifications, according to emerging evidence, perform a critical role for cellular immune response and tumorigenesis. Nonetheless, the role of N6-methyladenosine modification in shaping of the glioblastoma tumor microenvironment is unknown. Methods: N6-methyladenosine(m6A) methylation patterns in GBM patients were evaluated via multiple omics analysis of 15 m6A regulators and systematically correlated with tumor immune features. For quantification of N6-methyladenosine methylation patterns of individual patients, GM-score was developed and correlated with clinical and immunological characteristics. Results: Glioblastoma has two different m6A methylation patterns that are strongly associated with TME characteristics, tumor subtype, immunotherapy response, and patient prognosis. High-GM-score is associated with an immune tolerance phenotype dominated by the IDH1 wild molecular subtype and the Mesenchymal tissue subtype, as well as a high infiltration of immune cells and stromal cells and a poor prognosis. Furthermore, despite higher immune checkpoint expression, individuals with a high-GM-score have a poorer response to anti-CTLA4 immunotherapy regimens due to T-cells dysfunctional. Low-GM-score individuals had an immunodeficient phenotype dominated by IDH mutant molecular subtypes and Proneural tissue subtypes, with less immune cell infiltration and a better prognosis. Furthermore, patients with low-GM-scores had higher microsatellite instability (MSI) and t-cell exclusion scores, as well as a better response to anti-CTLA4 immunotherapy regimens. Conclusion: This study demonstrated that m6A modification patterns play an important role in the shaping of TME complexity and diversity. The GM-score could identify m6A modification patterns in individual patients, resulting in a more personalization and efficacious anti-tumor immunotherapy strategy.


Assuntos
Glioblastoma , Microambiente Tumoral , Adenosina/análogos & derivados , Adenosina/metabolismo , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Metilação , Microambiente Tumoral/genética
8.
World Allergy Organ J ; 15(8): 100674, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36017065

RESUMO

Background: Nasal microbiota is crucial for the pathogenesis of allergic rhinitis (AR), which has been reported to be different from that of healthy individuals. However, no study has investigated the microbiota in nasal extracellular vesicles (EVs). We aimed to compare the microbiome composition and diversity in EVs between AR patients and healthy controls (HCs) and reveal the potential metabolic mechanisms in AR. Methods: Eosinophil counts and serum immunoglobulin E (IgE) levels were measured in patients with AR (n = 20) and HCs (n = 19). Nasal EVs were identified using transmission electron microscopy and flow cytometry. 16S rRNA sequencing was used to profile the microbial communities. Alpha and beta diversities were analyzed to determine microbial diversity. Taxonomic abundance was analyzed based on the linear discriminant analysis effect size (LEfSe). Microbial metabolic pathways were characterized using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUst2) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Eosinophils, total serum IgE, and IgE specific to Dermatophagoides were increased in patients with AR. Alpha diversity in nasal EVs from patients with AR was lower than that in HCs. Beta diversity showed microbiome differences between the AR and HCs groups. The microbial abundance was distinct between AR and HCs at different taxonomic levels. Significantly higher levels of the genera Acetobacter, Mycoplasma, Escherichia, and Halomonas were observed in AR patients than in HCs. Conversely, Zoogloea, Streptococcus, Burkholderia, and Pseudomonas were more abundant in the HCs group than in the AR group. Moreover, 35 microbial metabolic pathways recognized in AR patients and HCs, and 25 pathways were more abundant in the AR group. Conclusion: Patients with AR had distinct microbiota characteristics in nasal EVs compared to that in HCs. The metabolic mechanisms of the microbiota that regulate AR development were also different. These findings show that nasal fluid may reflect the specific pattern of microbiome EVs in patients with AR.

9.
Int J Soc Psychiatry ; 67(4): 344-350, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32815434

RESUMO

OBJECTIVES: The COVID-19 pandemic has caused a profound impact on health and well-being of populations. However, there are limited studies that have investigated the psychological aspects of vulnerable groups including pregnant women amid the COVID-19 pandemic. Therefore, we aimed to assess the psychological impact of the COVID-19 pandemic among Chinese pregnant women from February 2020 until March 2020. METHODS: Our study was conducted using a modified validated online questionnaire comprising of sociodemographic, the Impact of Event Scale (IES), attitude and mental health-related questions towards COVID-19. RESULTS: A total of 560 women were included. The overall mean age and IES of women was 25.8 ± 2.7 years and 31.4 ± 13.7. Moreover, 67.1% of them had IES ⩾26. Psychological impact seemed to be more severe in women in second trimester of pregnancy (the highest IES) (p = .016). There was a significant association between trimesters of pregnancy and some indicators of negative health impacts (including increased stress from work, increased stress from home, feeling apprehensive and helpless during the early stages of the COVID-19 pandemic) (all p < .05). CONCLUSIONS: Our results reported moderate-to-severe stressful impact among Chinese pregnant women. We recommend that appropriate measures should be taken to address the maternal mental health issues.


Assuntos
COVID-19/psicologia , Estilo de Vida , Saúde Mental , Gestantes/psicologia , Estresse Psicológico , Adulto , China , Estudos Transversais , Feminino , Humanos , Gravidez , Apoio Social , Inquéritos e Questionários , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-32244498

RESUMO

Our study aimed to investigate the immediate impact of the COVID-19 pandemic on mental health and quality of life among local Chinese residents aged ≥18 years in Liaoning Province, mainland China. An online survey was distributed through a social media platform between January and February 2020. Participants completed a modified validated questionnaire that assessed the Impact of Event Scale (IES), indicators of negative mental health impacts, social and family support, and mental health-related lifestyle changes. A total of 263 participants (106 males and 157 females) completed the study. The mean age of the participants was 37.7 ± 14.0 years, and 74.9% had a high level of education. The mean IES score in the participants was 13.6 ± 7.7, reflecting a mild stressful impact. Only 7.6% of participants had an IES score ≥26. The majority of participants (53.3%) did not feel helpless due to the pandemic. On the other hand, 52.1% of participants felt horrified and apprehensive due to the pandemic. Additionally, the majority of participants (57.8-77.9%) received increased support from friends and family members, increased shared feeling and caring with family members and others. In conclusion, the COVID-19 pandemic was associated with mild stressful impact in our sample, even though the COVID-19 pandemic is still ongoing. These findings would need to be verified in larger population studies.


Assuntos
Infecções por Coronavirus/psicologia , Medo , Saúde Mental , Pandemias , Pneumonia Viral/psicologia , Qualidade de Vida , Estresse Psicológico , Adulto , Ansiedade/epidemiologia , Povo Asiático , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/complicações , Estudos Transversais , Emoções , Família , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , SARS-CoV-2 , Apoio Social , Inquéritos e Questionários , Adulto Jovem
11.
Hum Ecol Interdiscip J ; 48(6): 749-756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33199934

RESUMO

We designed a self-administered 20-item questionnaire to determine changes in attitudes towards wildlife consumption in Chinese adults during the SARS epidemic in 2002-2003 and on-going COVID-19 pandemic that was first identified in December 2019. A total of 348 adults (177 males and 171 females) with a mean age of 29.4 ± 8.5 years participated, the majority (66.7%) from Hubei. The percentages of participants who had eaten wildlife significantly decreased from 27.0% during SARS to 17.8% during COVID-19 (P = 0.032). The most common reason participants provided for consuming wildlife was to try something novel (64.9% during SARS and 54.8% during COVID-19). More than half of participants (≥53.5%) reported that they had stopped eating wildlife meat because most species of wildlife are legally protected. Our study results indicate over the period between the SARS epidemic to the outbreak of the COVID-19 pandemic, attitudes towards the consumption of wildlife in China have changed significantly.

12.
Int J Soc Psychiatry ; 66(8): 770-779, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32564637

RESUMO

OBJECTIVES: Our study aimed to determine the impact of the COVID-19 pandemic on psychological responses and lifestyle changes among the general population in mainland China following the re-opening of the Wuhan city. METHODS: A cross-sectional survey was conducted in April 2020. Participants of Chinese nationality aged ⩾ 18 years were asked to complete a modified validated Chinese version of a questionnaire regarding the impact of event scale (IES), family and social support, mental health-related lifestyle changes, and indicators of negative mental health impacts. RESULTS: A total of 728 participants (i.e., 217 males and 511 females) completed the questionnaire. The mean age of the participants was 32.9 ± 10.4 years, with a majority of them (92.2%) having a higher educational qualification level. The overall mean IES in participants was 21.5 ± 7.0, reflecting mild stressful impact (i.e., following the re-opening of the Wuhan city); 25.5% of the participants had an IES score ⩾ 26. Being females and married were significantly associated with a higher mean IES score. The overall mean scores for intrusion and avoidance score scales in participants were 9.4 ± 3.7 and 12.1 ± 4.2, respectively. CONCLUSIONS: The COVID-19 pandemic was associated with increased stressful impact in our participants following the re-opening of the Wuhan city when compared with our previous study, which should not be taken lightly.


Assuntos
Infecções por Coronavirus/psicologia , Saúde Mental , Pneumonia Viral/psicologia , Qualidade de Vida/psicologia , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Betacoronavirus , COVID-19 , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Apoio Social , Inquéritos e Questionários , Adulto Jovem
13.
Nanoscale ; 12(7): 4729-4735, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32049081

RESUMO

Organic electrode materials have secured a distinctive place among the auspicious choices for modern energy storage systems due to their resource sustainability and environmental friendliness. Herein, a novel all-organic electrode-based sodium ion full battery is demonstrated using 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTCDA) as raw material for the assembly of positive and negative electrodes. Both the electrodes exhibit excellent cycling stability and rate performance. The fabricated organic sodium ion full battery not only displays a high initial capacity of 157 mA h g-1 with an average battery voltage of 1.47 V under the current density of 100 mA g-1, but also delivers a high energy density of 254 W h kg-1 and a high power density of 614 W kg-1. These sodium ion batteries with organic positive and negative electrode materials can provide a new way for energy storage devices.

14.
Physiol Behav ; 212: 112709, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655082

RESUMO

Maternal high-fat (HF) diet affects offspring's metabolic phenotype. Sweet taste is an important factor in promoting appetite. In order to determine the effects of maternal HF diet throughout gestation and lactation on taste sensitivity to sucrose in rat offspring, we measured conditioned aversion threshold for sucrose by conditioned taste aversion (CTA) associated with two-bottle choice tests, and measured mRNA expression of sweet taste receptors in taste buds. In male offspring, conditioned aversion threshold for sucrose lay between 0.007 M and 0.009 M in control group, while in those with HF dams, the threshold significantly increased to be between 0.011 M and 0.02 M. In female offspring, conditioned aversion threshold for sucrose lay between 0.003 M and 0.005 M in control group, whereas maternal HF diet increased it to be between 0.007 M and 0.009 M. Maternal HF diet increased T1R2 and T1R3 mRNA expression in taste buds of male offspring, while only increased T1R2 mRNA expression in female offspring. Both male and female offspring with HF dams had lower α-gustducin mRNA expression, whereas only male offspring with HF dams had lower OB-Rb mRNA expression in taste buds. Our data suggest that maternal HF diet decreased taste sensitivity to sucrose in both male and female offspring, which may be partly due to altered expression of sweet taste receptors and related downstream pathways in taste buds.


Assuntos
Aprendizagem da Esquiva/fisiologia , Dieta Hiperlipídica , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Limiar Gustativo/fisiologia , Paladar/fisiologia , Animais , Comportamento de Escolha/efeitos dos fármacos , Feminino , Lactação , Masculino , Gravidez , Ratos , Receptores Acoplados a Proteínas G/biossíntese , Fatores Sexuais , Sacarose/farmacologia , Paladar/efeitos dos fármacos , Papilas Gustativas/metabolismo , Papilas Gustativas/fisiologia , Transducina/biossíntese
15.
Oncol Rep ; 41(1): 15-26, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30542733

RESUMO

Recently, LOC285194 has shown a potential tumor-suppressor function in several types of human cancers, but its function in non-small cell lung cancer (NSCLC) remains unknown. This study intended to investigate the biological role of LOC285194 and its clinical significance in NSCLC. LOC285194 was detected by qRT-PCR, and its correlation with clinicopathological features of NSCLC was analyzed. The expression of LOC285194 was knocked down or ectopically expressed in lung cancer cells (A549 and H1299) and tumor cell growth, migration and invasion in vitro were investigated. In addition, the interaction of LOC285194 and target proteins was assessed by RNA pulldown and RNA immunoprecipitation in vitro. The results revealed that the expression of LOC285194 was significantly lower in tumor tissues when compared with the corresponding non-tumor tissues (P<0.001). Its expression was correlated with the tumor size (P=0.027). Kaplan-Meier analysis revealed that patients with lower LOC285194 expression had worse disease-free survival and overall survival rates (P<0.05). RNA protein interaction analysis revealed that p53 was the direct binding target of LOC285194 in NSCLC. Bioinformatics analyses suggested that depletion of LOC285149 could affect its antitumor function through the KRAS/BRAF/SMEK pathway. Our findings indicated that LOC285194 was a novel non-coding prognostic indicator and contributed to tumor suppression by targeting p53 in NSCLC, suggesting that it may be a non-coding target for NSCLC gene therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , RNA Longo não Codificante/metabolismo , Proteína Supressora de Tumor p53/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Genes Supressores de Tumor , Humanos , Estimativa de Kaplan-Meier , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Taxa de Sobrevida , Proteína Supressora de Tumor p53/metabolismo
16.
J Exp Clin Cancer Res ; 34: 118, 2015 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-26458953

RESUMO

BACKGROUND: Tivantinib has been described as a highly selective inhibitor of MET and is currently in a phase III clinical trial for the treatment of hepatocellular carcinoma (HCC). However, the mechanism of tivantinib anti-tumor effect has been questioned by recent studies. RESULTS: We show that tivantinib indiscriminately inhibited MET dependent and independent HCC cells proliferation. In contrast, other MET inhibitors, JNJ-38877605 and PHA-665752, just specifically inhibited the growth of MET dependent HCC cells. Tivantinib neither inhibit constitutive MET phosphorylation nor HGF-induced MET phosphorylation in HCC cells. In the microtubule polymerization analysis, tivantinib affected microtubule dynamics by a mechanism as a microtubule depolymerizer. Interesting, unlike other microtubule-targeting agents, paclitaxel and vincristine, tivantinib showed similar anti-proliferative activity in parental and multidrug-resistant cells. Further studies demonstrated that tivantinib induced a G2/M arrest and promoted apoptosis by both intrinsic and extrinsic pathway. The in vivo efficacy evaluation showed that tivantinib exhibited a good anti-tumor growth activity with anti-proliferative and pro-apoptotic effects. CONCLUSIONS: The potent anti-tumor activity of tivantinib in HCC was achieved by targeting microtubule. Tivantinib treatment for patients with HCC should not be selected based on MET status.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Pirrolidinonas/farmacologia , Quinolinas/farmacologia , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/biossíntese , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Células HEK293 , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microtúbulos/metabolismo , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/genética , Interferência de RNA , RNA Interferente Pequeno , Ensaios Antitumorais Modelo de Xenoenxerto
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