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1.
J Transl Med ; 19(1): 347, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389031

RESUMO

BACKGROUND: Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM. METHODS: TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages. RESULTS: We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages. CONCLUSIONS: Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Linhagem Celular Tumoral , Humanos , Ferro , Camundongos , Macrófagos Associados a Tumor
2.
ACS Appl Mater Interfaces ; 13(25): 29416-29423, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34148345

RESUMO

DNA self-assembled nanostructures have been considered as effective vehicles for biomolecule delivery because of their excellent biocompatibility, cellular permeability, noncytotoxicity, and small size. Here, we report an efficient antiviral strategy with self-assembled tetrahedral framework nucleic acids (tFNAs) delivering small interfering RNA (t-siRNA) to silence classical swine fever virus (CSFV) gene in porcine host cells. In this study, two previously reported siRNAs, C3 and C6, specifically targeting the CSFV genome were selected and modified on tFNAs, respectively, and termed t-C3 and t-C6. Results indicate that t-C3 and t-C6 can inhibit the viral proliferation of CSFV in kidney derived porcine cells, PK-15, effectively and that inhibition was markedly stronger than free siRNA-C3 or siRNA-C6 only. In addition, the DNA nanostructure also has high cargo-carrying capacity, allowing to deliver multiple functional groups. To improve the antiviral ability of tFNAs, a dual-targeting DNA nanostructure t-C3-C6 was constructed and used to silence the CSFV gene in porcine host cells. This study found that t-C3-C6 can inhibit the viral release and replication, exhibiting outstanding anti-CSFV capabilities. Therefore, these dual-targeting tFNAs have great potential in virus therapy. This strategy not only provides a novel method to inhibit CSFV replication in porcine cells but also verifies that tFNAs are effective tools for delivery of antiviral elements, which have great application potential.


Assuntos
Antivirais , Vírus da Febre Suína Clássica/efeitos dos fármacos , Portadores de Fármacos , Nanoestruturas/química , RNA Interferente Pequeno , Animais , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , Linhagem Celular , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Suínos , Replicação Viral/efeitos dos fármacos
3.
Adv Healthc Mater ; 9(21): e2000650, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33000919

RESUMO

Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), reveals a limited therapeutic effect due to a lack of selectivity and evident drug resistance. In the present study, bismuth-based mesoporous nanomaterial (NBOF) is loaded with SOR and then coated with polyethylene glycol and folic acid conjugates (P-FA) to form an NBOF@SOR-P-FA nanocarrier system. The system achieves significantly enhanced anti-cancer efficacy by combining chemotherapy with radiotherapy. To evaluate the effect of synergistic treatment, cytotoxicity detection, Live/Dead staining, apoptotic assay, and Western blot analysis are performed. The results suggest that NBOF@SOR-P-FA significantly inhibits HCC cell proliferation and promotes cell apoptosis. Also, the NBOF@SOR-P-FA exhibits excellent biocompatibility by hemolysis and serum biochemical tests and produces a substantially enhanced contrast efficiency as compared to iohexol by computed tomography imaging. More importantly, the profound suppression of tumor growth and potentiation of apoptosis are observed in a mouse subcutaneous tumor model. Collectively, these results indicate that the bismuth-based nanotheranostic platform could enhance the therapeutic effect of sorafenib and serve as an innovative method for HCC treatment.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Bismuto/farmacologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Quimiorradioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Niacinamida , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico
4.
Oncogene ; 39(35): 5768-5781, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32719439

RESUMO

Cumulative evidence suggests that microRNAs (miRNAs) promote gene expression in cancers. However, the pathophysiologic relevance of miRNA-mediated RNA activation in hepatocellular carcinoma (HCC) remains to be established. Our previous miRNA expression profiling in seven-paired HCC specimens revealed miR-93-5p as an HCC-related miRNA. In this study, miR-93-5p expression was assessed in HCC tissues and cell lines by quantitative real-time PCR and fluorescence in situ hybridization. The correlation of miR-93-5p expression with survival and clinicopathological features of HCC was determined by statistical analysis. The function and potential mechanism of miR-93-5p in HCC were further investigated by a series of gain- or loss-of-function experiments in vitro and in vivo. We identified that miR-93-5p, overexpressed in HCC specimens and cell lines, leads to poor outcomes in HCC cases and promotes proliferation, migration, and invasion in HCC cell lines. Mechanistically, rather than decreasing target mRNA levels as expected, miR-93-5p binds to the 3'-untranslated region (UTR) of mitogen-activated protein kinase kinase kinase 2 (MAP3K2) to directly upregulate its expression and downstream p38 and c-Jun N-terminal kinase (JNK) pathway, thereby leading to cell cycle progression in HCC. Notably, we also demonstrated that c-Jun, a downstream effector of the JNK pathway, enhances miR-93-5p transcription by targeting its promoter region. Besides, downregulation of miR-93-5p significantly retarded tumor growth, while overexpression of miR-93-5p accelerated tumor growth in the HCC xenograft mouse model. Altogether, we revealed a miR-93-5p/MAP3K2/c-Jun positive feedback loop to promote HCC progression in vivo and in vitro, representing an RNA-activating role of miR-93-5p in HCC development.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MAP Quinase Quinase Quinase 2/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Regiões 3' não Traduzidas , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MAP Quinase Quinase Quinase 2/biossíntese , MAP Quinase Quinase Quinase 2/genética , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Fosforilação , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-jun/genética , Transfecção , Regulação para Cima
6.
Ann Surg Oncol ; 27(5): 1546-1557, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32157528

RESUMO

BACKGROUND: The mechanistic target of rapamycin (mTOR) pathway, containing mTOR complex 1 (mTORC1) and mTORC2, is dysregulated in multiple cancers, including hepatocellular carcinoma (HCC). Mammalian lethal with sec-13 protein 8 (mLST8) is a shared constituent of both mTORC1 and mTORC2, yet little is known regarding its role in HCC development. METHODS: mLST8 expression was detected in a total of 186 pairs of HCC and adjacent non-tumor specimens. The correlation between mLST8 level and clinicopathological features or prognostic significance were analyzed. The role of mLST8 on biological functions was also preliminarily studied. RESULTS: The study revealed that the mLST8 level was dramatically higher in HCC specimens than in adjacent non-tumor specimens. mLST8 overexpression positively correlated with tumor size, differentiation, and vessel invasion. Cases with elevated mLST8 level had more unfavorable overall survival (OS) and disease-free survival (DFS) than those with downregulated mLST8 level. Multivariate analysis demonstrated that mLST8 upregulation was an independent predictive marker for OS and DFS. Calibration curves from nomogram models indicated an excellent coherence between nomogram prediction and actual situation. Decision curve analysis proved that mLST8-based nomograms presented much higher predictive accuracy when compared with conventional clinical staging systems. Mechanistically, mLST8 enhanced cell proliferation and invasion through the AKT (protein kinase B) pathway. CONCLUSIONS: Our study demonstrates that mLST8 exerts an oncogenic role in HCC and may become a promising prognostic biomarker and therapeutic target for HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Homólogo LST8 da Proteína Associada a mTOR/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Prognóstico , Regulação para Cima , Adulto Jovem
7.
ACS Appl Mater Interfaces ; 12(15): 17193-17206, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32207914

RESUMO

Sorafenib, a multitargeted kinase inhibitor, has been reported to elicit a limited therapeutic effect in hepatocellular carcinoma (HCC). Currently, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful modality for cancer therapy. However, few studies have been reported the effectiveness of the combination of sorafenib with PDT and PTT in HCC. Herein, we designed and synthesized bovine serum albumin (BSA)-coated zinc phthalocyanine (ZnPc) and sorafenib (SFB) nanoparticle (ZnPc/SFB@BSA). The obtained ZnPc/SFB@BSA was able to trigger PDT, PTT, and chemotherapy. After irradiation by a 730 nm light, ZnPc/SFB@BSA significantly suppressed HCC cell proliferation and metastasis while promoted cell apoptosis in vitro. Furthermore, intravenous injection of ZnPc/SFB@BSA led to dramatically reduced tumor growth in an orthotopic xenograft HCC model. More importantly, ZnPc/SFB@BSA presented low toxicity and adequate blood compatibility. Therefore, a combination of ZnPc with sorafenib via BSA-assembled nanoparticle can markedly suppress HCC growth, representing a promising strategy for HCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Indóis/química , Neoplasias Hepáticas/terapia , Nanocápsulas/química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/uso terapêutico , Sorafenibe/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Indóis/metabolismo , Indóis/uso terapêutico , Luz , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Camundongos , Camundongos Nus , Compostos Organometálicos/metabolismo , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Espécies Reativas de Oxigênio , Soroalbumina Bovina/química , Sorafenibe/metabolismo , Sorafenibe/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Aging (Albany NY) ; 12(3): 2373-2392, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012120

RESUMO

Upregulated ubiquitin-conjugating enzyme E2M (UBE2M) is associated with poor prognosis in malignancies; However, the phenotype and mechanism of action of UBE2M in hepatocellular carcinoma (HCC) remain elusive. Here, we report that UBE2M is overexpressed and correlated with poor prognosis in HCC patients. The UBE2M level is an independent prognostic factor for HCC patients. UBE2M knockdown inhibits HCC cell proliferation, migration, and invasion, whereas its overexpression has an opposite effect. Mechanistically, upregulated UBE2M exerts oncogenic effects by translocation of accumulated ß-catenin from the cytoplasm to the nucleus, thus activating downstream ß-catenin/cyclin D1 signaling. In summary, our study demonstrates a notable role of UBE2M in promoting the growth of HCC, providing a novel strategy for HCC prevention and treatment.


Assuntos
Carcinoma Hepatocelular/patologia , Ciclina D1/metabolismo , Neoplasias Hepáticas/patologia , Enzimas de Conjugação de Ubiquitina/metabolismo , beta Catenina/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Proliferação de Células/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais/fisiologia
9.
J Matern Fetal Neonatal Med ; 33(4): 547-552, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30185086

RESUMO

Objective: To analyze the clinical characteristics and prognosis of anorectal malformations (ARMs) and explore the influencing factors of postoperative anal function in Anhui Province of China.Methods: We performed a retrospective study of ARM patients diagnosed from 2013 to 2016 at Anhui Provincial Children's Hospital. A total of 332 infants with ARM were enrolled in the survey. Demographic characteristic and clinical data were collected. Follow-up study was required to evaluate anal function after the operation and Logistic regression analysis was used for analyzing the influencing factors of prognosis.Results: A total of 253 males and 79 females were studied, with a ratio of 3.2:1. Abdominal distention was the most common presenting symptom, followed by vomiting. Of the cases, 53.0% (176/332) combined with other congenital malformations. The incidence of other malformations in intermediate and high ARM group was significantly higher than that in the low ARM group. Of the cases, 280 underwent anoplasty. 188, 73, 19 cases were treated with one-stage perineal anoplasty, posterior sagittal anorectoplasty, laparoscopically assisted anorectal pull-through, respectively. The result of follow-up study showed that the excellent and good rate of postoperative anal function was up to 83.3%. Type of ARM, combined with other malformations and the times of anoplasty were related to the anal function postoperatively.Conclusions: ARM occurs mainly in male infants. The incidence of associated abnormalities in ARM patients was high. Intermediate- and high-type, combined with other malformations and more times of anoplasty increased the risk of anal dysfunction postoperatively. Multicenter, prospective randomized-controlled studies were needed to clarify the curative effect of different surgical approaches.


Assuntos
Malformações Anorretais/epidemiologia , Malformações Anorretais/cirurgia , China/epidemiologia , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos
10.
J Cell Biochem ; 121(4): 2938-2949, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31692072

RESUMO

BACKGROUND: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR-a/b (combined CABYR-a and CABYR-b), in HCC remain to be established. METHODS: CABYR-a/b expression was detected in HCC tissues and cell lines by quantitative real-time polymerase chain reaction and Western blot analysis. The correlation of CABYR-a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR-a/b were also investigated using molecular biology approaches. RESULTS: The present research found that CABYR-a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR-a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR-a/b level had poorer overall survival (OS) and disease-free survival (DFS) than those with reduced CABYR-a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR-a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR-a/b downregulation suppressed cell proliferation and induced G1-phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B-cell lymphoma 2 (Bcl-2) and increasing Bcl-2-associated death promoter. CONCLUSION: Our research indicates that CABYR-a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.


Assuntos
Apoptose , Proteínas de Ligação ao Cálcio , Cálcio/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Tirosina/química , Idoso , Processamento Alternativo , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Hepatocelular/diagnóstico , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Ligação Proteica , Isoformas de Proteínas , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/metabolismo , Resultado do Tratamento
11.
J Korean Acad Nurs ; 50(6): 778-786, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33441525

RESUMO

PURPOSE: This study aimed to explore the motives of clinical nurses for experiencing empathy with patients and their families based on a self-determination theory framework. METHODS: Semi-structured face-to-face interviews with twenty-one nurses at four tertiary hospitals in Anhui, China, were conducted, recorded and transcribed. A content analysis with a directed approach was performed. RESULTS: An analysis of the interview transcripts revealed three categories of empathy motivation: autonomous motivation, controlled motivation and a lack of empathy motivation. Autonomous motivation included personal interests, enjoyment and a sense of value, pure altruism, assimilation, and recognition of the importance of empathy. Controlled motivation highlighted pressures from oneself and others, the possibility of tangible or intangible rewards, and avoidance of adverse effects. Finally, a lack of empathy motivation referred to a lack of intention for empathy and denial of the value of empathy. CONCLUSION: This study provides a deep understanding of the motives underlying empathy in nurses. The results reveal the reasons for empathy and may support the development of effective strategies to foster and promote empathy in nurses.


Assuntos
Motivação , Enfermeiras e Enfermeiros , Empatia , Humanos , Autonomia Pessoal , Pesquisa Qualitativa
12.
Cancer Manag Res ; 11: 8359-8370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571992

RESUMO

Background: Growing evidence suggests that the ubiquitin-proteasome system is involved in the pathogenesis and recurrence of hepatocellular carcinoma (HCC); yet, little is known about the role of ubiquitin-conjugating enzyme E2T (UBE2T) in HCC. Materials and methods: UBE2T levels were detected in HCC tissues and hepatoma cell lines using quantitative reserve transcriptase-polymerase chain reaction and Western blot analysis. Next, the changes of phenotypes after UBE2T knockdown or overexpression were evaluated using in vitro methods. Finally, the mechanism of UBE2T in HCC was tested using ex vivo and in vivo methods. Results: In the present study, we reported that UBE2T mRNA and protein levels were significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Additionally, suppression of UBE2T expression inhibited proliferation, colony formation, tumorigenesis, migration, and invasion of hepatoma cells, whereas UBE2T overexpression led to the opposite outcomes. Moreover, suppression of UBE2T expression resulted in an increase in G2/M phase and a decrease in the percentage of cells in G1 phase, which indicated a cell cycle arrest at the G2/M phase. In contrast, the percentage of cells in G2/M phase decreased following UBE2T overexpression. Further study indicated that UBE2T regulated the G2/M transition by modulating cyclin B1 and cyclin-dependent kinase 1. Conclusion: Taken together, the findings of the present study uncover biological functions of UBE2T in hepatoma cells, and delineate preliminary molecular mechanisms of UBE2T in modulating HCC development and progression.

13.
Int J Mol Med ; 44(5): 1844-1854, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31485608

RESUMO

Long non­coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differentially expressed mRNAs. Cytoscape was applied to construct an lncRNA­miRNA­mRNA co­expression network and candidate lncRNAs were validated via quantitative PCR in 30 pairs of HCC and adjacent tumor­free tissues. In this study, 1,056 upregulated and 1,288 downregulated lncRNAs were identified, while 2,687 mRNAs and 6 miRNAs were aberrantly expressed in HCC compared with adjacent tumor­free tissues. Potential functions of differentially expressed mRNAs were demonstrated to significantly participate in modulating critical genes in the cell cycle, such as cyclin E1 and cyclin B2. After screening, 95 lncRNAs, 5 miRNAs and 36 mRNAs were recruited for construction of lncRNA­mRNA­miRNA co­expression network in the cell cycle pathway. Subsequently, the top 5 lncRNAs that potentially modulate critical genes in the cell cycle were selected as the candidates for further verification. Kaplan­Meier curves using the Cancer Genome Atlas database showed that 13 targeted mRNAs were associated with overall survival of HCC patients. Finally, three lncRNAs, including ENST00000522221, lnc­HACE1­6:1 and lnc­ICOSLG­11:1, are significantly upregulated in HCC tissues compared with adjacent tumor­free tissues. These findings suggest that lncRNAs play essential roles in the pathogenesis of HCC via regulating coding genes and miRNAs, and may be important targets for diagnosis and treatment of this disease.


Assuntos
Carcinoma Hepatocelular/genética , Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade
14.
Cancer Manag Res ; 11: 2927-2934, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114341

RESUMO

Background: Aberrant expression of pepsinogen C (PGC) has been observed in human cancers. However, its role in hepatocellular carcinoma (HCC) remains to be established. The goal of this study is to illustrate PGC expression and to evaluate its clinical relevance in HCC. Materials and methods: PGC expression was examined in 75 pairs of HCC and adjacent non-tumor tissues using tissue microarray. The correlations between its expression and clinical parameters were also analyzed. Results: PGC overexpression was significantly associated with larger tumor size (≥5 cm; P=0.017) and incomplete encapsulation (P<0.0001). Cox regression model demonstrated that PGC expression and tumor size were independent prognostic factors for overall survival (OS) and disease-free survival (DFS) in HCC. The subgroup analysis by Kaplan-Meier uncovered that OS and DFS were much worse in high PGC level group than in low PGC level group with large tumor size subgroup, while no difference of OS was noted between the two groups with low tumor size subgroup. Conclusion: PGC plays a tumorigenesis role in HCC progression, which may lead to a novel insight to the potential biomarker and novel therapeutic strategies for HCC patients.

15.
Biochim Biophys Acta Rev Cancer ; 1871(2): 379-391, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30951815

RESUMO

The mechanistic target of rapamycin (mTOR) pathway coordinates organismal growth and homeostasis in response to growth factors, nutrients, and cellular energy stage. The pathway regulates several major cellular processes and is implicated in various pathological conditions, including hepatocellular carcinoma (HCC). This review summarizes recent advances of the mTOR pathway, highlights the potential of the mTOR pathway as a therapeutic target, and explores clinical trials targeting the mTOR pathway in HCC. Although the review focuses on the mTOR pathway involved in HCC, more comprehensive discussions (eg, developing a rational design for future trials targeting the mTOR pathway) are also applicable to other tumors.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Humanos , Transdução de Sinais/fisiologia
16.
J Clin Nurs ; 28(13-14): 2599-2612, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30830708

RESUMO

AIMS AND OBJECTIVES: To develop and validate an instrument to measure nurses' empathy motivation in China (See Supporting Information Appendix S1). BACKGROUND: Nurses are increasingly expected to empathise with patients in clinical settings. However, research investigating nurses' empathy motivation in China is lacking, and no specific instrument exists worldwide. DESIGN: Two-stage cross-sectional study, which follows the STROBE guidelines. Instrument development and psychometric evaluation were used (See Supporting Information Appendix S1). METHODS: A literature review and qualitative interviews with nurses were conducted to generate the initial items. Convenience samples of 340 (for item analysis) and 640 (for psychometric evaluation) clinical nurses working at four tertiary hospitals in Anhui Province were recruited. The scale was validated by content validity, surface validity and item analysis. A total of 640 participants were randomly divided into two equal groups. Exploratory factor analysis (EFA) was used with varimax rotation, confirmatory factor analysis (CFA) and internal consistency reliability to analyse the psychometric properties of the scale (See Supporting Information Appendix S1). RESULTS: From the initial 90-item pool, 27 items were retained by the item analysis. The EFA (N = 290) showed the following six factors on the scale explained 71.266% of the overall variance: amotivation, external regulation, introjected regulation, identified regulation, integrative regulation and intrinsic motivation. Furthermore, when limited to three factors, that is autonomy motivation, controlled motivation and amotivation, 56.578% of the variance was explained. The findings showed high internal consistency. The six-factor solution and three-factor solution of the scale, including 27 items, were both confirmed by the CFA, for example χ2 /df = 1.744, 2.261; RMSEA = 0.051, 0.066; GFI = 0.882, 0.847; TLI = 0.942, 0.902; and RMR = 0.039, 0.049, respectively. CONCLUSIONS: The nurses' empathy motivation scale presents good psychometric properties and can be used to explore nurses' empathy motivation in China (See Supporting Information Appendix S1). RELEVANCE TO CLINICAL PRACTICE: This study offers insight into nurses' complicated reasons for exhibiting empathy.


Assuntos
Empatia , Relações Enfermeiro-Paciente , Recursos Humanos de Enfermagem no Hospital/psicologia , Inquéritos e Questionários/normas , Adulto , China , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Motivação , Psicometria , Reprodutibilidade dos Testes , Adulto Jovem
17.
Biomed Pharmacother ; 105: 1147-1154, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30021351

RESUMO

microRNA-19a-3p (miR-19a-3p) has been reported to regulate cell proliferation in hepatocellular carcinoma (HCC), but its role in HCC metastasis remains unknown. In this study, miR-19a-3p was noted to be upregulated in HCC specimens and cell lines. Aberrant expression of miR-19a-3p stimulated HCC cell metastasis, and phosphatase and tensin homolog (PTEN) was shown to be a direct target of miR-19a-3p. miR-19a-3p-mediated HCC metastasis was reversed by restoration of PTEN or could be imitated by silencing of PTEN. Modulation of miR-19a-3p also altered expression of phosphorylated Akt, a downstream mediator of PTEN. Moreover, aberrant expression of miR-19a-3p induced sorafenib resistance by regulating the PTEN/Akt pathway. In conclusion, ectopic expression of miR-19a-3p contributes to HCC metastasis and chemoresistance by modulating PTEN expression and the PTEN-dependent pathways.


Assuntos
Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/biossíntese , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Transdução de Sinais/fisiologia
18.
Tohoku J Exp Med ; 245(2): 89-98, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29899182

RESUMO

Hepatocellular carcinoma (HCC) remains a major health problem for delayed diagnosis, inefficient surveillance and poor prognosis. Recent studies have indicated that non-coding RNAs contribute to the development of new strategies for diagnosis and treatment of HCC. In the present study, we employed 18 pairs of HCC and matched non-tumor tissues for the identification of differentially expressed microRNAs (miRNAs) in HCC, among which 7 paired specimens were selected randomly for microarray detection. Totally, twenty-three miRNAs were screened out to have statistically significant differences with the threshold of P < 0.01 and fold-change ≥ 2.0 or ≤ 0.5 using miRNA microarray. In the validation stage, two miRNAs exhibited higher expression levels in the HCC tissues compared with those in the matched non-tumor tissues, whereas the expression levels of ten miRNAs were lower in the HCC tissues than those in the matched non-tumor tissues. In further analysis, eight miRNAs, including miR-4270, miR-125b-5p, miR-199a-3p, miR-10a-5p, miR-424-5p, miR-195-5p, miR-106b-5p and miR-3651, were retained, when another constraint about the signal intensity of microarray probes was established. Among these miRNAs, our study was the first to show the higher expression level of miR-3651 and the lower expression level of miR-4270 in HCC. The areas under the receiver-operating-characteristic curve values of miR-3651 and miR-4270 were 0.730 and 0.967, respectively, indicating their potential diagnostic values. Our results may help provide the context for expanded interpretations of miRNA studies involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , MicroRNAs/genética , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
J Matern Fetal Neonatal Med ; 31(20): 2742-2747, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28701060

RESUMO

OBJECTIVE: To analyze the clinical and epidemiological features of patients with infantile hypertrophic pyloric stenosis (IHPS) so as to provide scientific evidence for diagnosis and prevention of IHPS. METHODS: We performed a retrospective study of infants with IHPS diagnosed from 2012 to 2015 at Anhui Provincial Children's Hospital. Demographic characteristics and clinical data were collected. RESULTS: Three hundred four patients (264 males and 40 females) were studied, of which 94.7% were full term and 75.7% were bottle fed or mixed fed; 16.8% of the patients had other congenital malformations in combination with IHPS. The proportion of IHPS cases with hyponatremia, hypokalemia, and hypochloremia was 18.4%, 12.5%, and 53.9%. A negative correlation was found between duration of disease and serum electrolytes. The mean pyloric muscle thickness, pyloric length, and diameter were 4.8 ± 0.7 mm, 19.4 ± 2.5 mm, and 13.3 ± 1.8 mm, respectively. There were significant differences in muscle thickness, pyloric length, and diameter between short (≤14 d) and long (>14 d) durations of disease. All patients underwent pyloromyotomy, and postoperative recovery was good. CONCLUSIONS: IHPS occurs mainly in male, full-term, bottle-fed or mixed-fed infants. Patients with long duration of disease were more likely to develop electrolyte disorder and thicker muscle layer. More attention should be paid to early discovery and diagnosis, which will help to improve the curative effect and prognosis of IHPS.


Assuntos
Estenose Pilórica Hipertrófica/epidemiologia , China/epidemiologia , Eletrólitos/sangue , Feminino , Humanos , Recém-Nascido , Masculino , Estenose Pilórica Hipertrófica/sangue , Estenose Pilórica Hipertrófica/diagnóstico por imagem , Estenose Pilórica Hipertrófica/cirurgia , Piloromiotomia , Estudos Retrospectivos , Ultrassonografia
20.
Cancer Lett ; 400: 175-182, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28461246

RESUMO

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide. However, current strategies curing HCC are far from satisfaction. The Hippo pathway is an evolutionarily conserved tumor suppressive pathway that plays crucial roles in organ size control and tissue homeostasis. Its dysregulation is commonly observed in various types of cancer including HCC. Recently, the prominent role of non-coding RNAs in the Hippo pathway during normal development and neoplastic progression is also emerging in liver. Thus, further investigation into the regulatory network between non-coding RNAs and the Hippo pathway and their connections with HCC may provide new therapeutic avenues towards developing an effective preventative or perhaps curative treatment for HCC. Herein we summarize the role of non-coding RNAs in the Hippo pathway, with an emphasis on their contribution to carcinogenesis, diagnosis, treatment and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Serina-Treonina Quinases/genética , RNA não Traduzido/genética , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Técnicas de Diagnóstico Molecular , Valor Preditivo dos Testes , Prognóstico , Proteínas Serina-Treonina Quinases/metabolismo , RNA não Traduzido/metabolismo , Transdução de Sinais
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