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1.
BMC Oral Health ; 23(1): 679, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726764

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an invasive cancer with a high recurrence rate. Most clinical studies have focused on the prognosis of patients with OSCC, few have investigated the causes and interventions that affect the recurrence. Our study is to explore the temporal and spatial patterns of recurrence in OSCC. METHODS: 234 OSCC patients with recurrence in our hospital and 64 OSCC patients with recurrence in TCGA database were included in the study. Log-rank test and Multivariate Cox Regression Analysis were used to determine whether there was a significant difference between each selected demographic or clinical factors and recurrence. The Kaplan-Meier method was used to plot survival curves for each recurrence interval. RESULTS: The proportion of OSCC patients in clinical and TCGA with early recurrence was 93.6% and 84.4%, respectively. Age, chewing betel nut, previous radiotherapy, histopathological grading of the primary tumor (poorly differentiated), lymph node metastasis and postoperative infection were found to be associated with the timing of recurrence. It was found that tongue cancer has more regional recurrences, while buccal cancer is mostly local and loco-regional recurrences. The earlier the recurrence, the greater the possibility of local-regional recurrence and the worse the prognosis. CONCLUSION: Most of recurrent OSCC patients present early recurrence (< 18 months) with poor prognosis, and early recurrence is more prone to local recurrence. Moreover, recurrence site is related with primary site of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/epidemiologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , China/epidemiologia
2.
J Proteomics ; 288: 104979, 2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37524227

RESUMO

Aging is accompanied by deterioration in physical condition, and creates high risks of diseases. Stem cell therapy exhibited promising potential in delaying aging. However, the unelucidated therapeutic mechanism limits future clinical application. Herein, to systematically understand the response to stem cell transfusion at the molecular level, we performed quantitative serum proteomic and peptidomics analyses in the 24-month-old aging mice model with or without mesenchymal stem cell (MSC) treatment. As a result, a total of 560 proteins and 2131 endogenous peptides were identified, among which, 6 proteins and 9 endogenous peptides derived from 6 precursor proteins were finally identified as therapeutic biomarkers after MSC transfusion on aging mice both by untargeted label-free quantification and targeted parallel reaction monitoring (PRM) quantification. Amazingly, the biological function of these differential proteins was mainly related to inflammation, which is not only the important hallmark of aging, but also the main cause of inducing aging. The reduction of these inflammatory protein content after MSC treatment further suggests the anti-inflammatory effect of MSC therapy reported elsewhere. Therefore, our study provides new evidence for the anti-inflammatory effect of MSC therapy for anti-aging and offers abundant data to support deeper investigations of the therapeutic mechanism of MSC in delaying aging.


Assuntos
Células-Tronco Mesenquimais , Proteômica , Humanos , Camundongos , Animais , Pré-Escolar , Anti-Inflamatórios/metabolismo , Células-Tronco Mesenquimais/metabolismo , Biomarcadores/metabolismo , Envelhecimento
3.
Appl Health Econ Health Policy ; 21(5): 773-783, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37356080

RESUMO

OBJECTIVE: This research assesses the cost effectiveness of Axicabtagene ciloleucel (Axi-cel), Tisagenlecleucel (Tis-cel), Relmacabtagene autoleucel (Rel-cel) and Lisocabtagene maraleucel (Lis-cel) against standard of care (SOC) for patients with diffuse large B-cell lymphoma (DLBCL) in the first-line setting (1L), second-line setting (2L) and third-line or later setting (3L+). METHODS: Markov modelling based on a flexible survival model was adopted to evaluate four chimeric antigen receptor T-cell (CAR-T) therapies compared with SOC for patients with diffuse large B-cell lymphoma (DLBCL). The clinical inputs and utility values of the model were derived from the most recent clinical trials and the health care costs from a Chinese provincial clinical center. Costs and quality-adjusted life years (QALYs) were used to derive incremental cost-effectiveness ratios (ICERs) from the Chinese health care system perspective. RESULTS: The ICER of Axi-cel (1L) versus SOC was approximately Chinese Yuan (CNY) 2,125,311 per QALY. The ICER for Axi-cel (2L), Tis-cel (2L) and Liso-cel (2L)) versus SOC in transplant-eligible patients were approximately CNY363,977, CNY32,066,781 and CNY347,746 per quality-adjusted life year (QALY), respectively. The ICER for Liso-cel (2L) versus SOC in transplant-ineligible patients was approximately CNY1,233,972 per QALY. The ICERs for Axi-cel (3L+), Tis-cel (3L+), Rel-cel (3L+) and Liso-cel (3L+) versus SOC were approximately CNY346,009, CNY654,344, CNY280,964 and CNY436,858 per QALY, respectively. In the scenario analysis using mixture cure models, the long-term survival benefit for CAR-T and SOC groups was found higher, and only Rel-cel (3L+) was found to be cost effective. CONCLUSION: Our results demonstrated that CAR-T treatments are not cost effective in any-line settings for DLBCL patients at the WHO-recommended willingness-to-pay threshold (CNY257,241 per QALY) in the base-case analysis. Price reduction of CAR-T therapies is the main approach for lowering ICERs and ensuring that the drug costs are proportional to patient health benefits.


Assuntos
Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Análise de Custo-Efetividade , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Terapia Baseada em Transplante de Células e Tecidos
4.
Ann Med ; 54(1): 3129-3135, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36345981

RESUMO

BACKGROUND: Paediatric pleural tuberculosis (TB) is a paucibacillary disease, which increases the difficulty of examination. We aimed to assess the performance of pleural fluid adenosine deaminase (ADA) in the detection of paediatric pleural TB. METHODS: PubMed, Web of Science Core Collection, Embase and Cochrane Library databases were searched up to 20 December 2021. We used the bivariate and hierarchical summary receiver operating characteristic models to compute pooled estimates for the overall diagnostic accuracy parameters of ADA for diagnosing paediatric pleural TB. RESULTS: Eight studies, including 290 pleural fluid samples, met the inclusion criteria. The pooled sensitivity of ADA was 0.85 (95% CI: 0.78-0.90, I2: 55.63% < 75%) for detecting patients with paediatric pleural TB. A total of 262 pleural fluid samples from four studies were included to differentiate patients with paediatric pleural TB from controls. At a unified cut-off value of 40 U/L, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the summary receiver operating characteristic curve of ADA were 0.89, 0.58, 2.09, 0.20, 10.48 and 0.89, respectively. CONCLUSIONS: At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity. Key messageAccurate identification of paediatric pleural TB will help eliminate TB in children. At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity.


Assuntos
Derrame Pleural , Tuberculose Pleural , Humanos , Criança , Tuberculose Pleural/diagnóstico , Adenosina Desaminase , Derrame Pleural/diagnóstico , Sensibilidade e Especificidade , Curva ROC
6.
Support Care Cancer ; 30(3): 2735-2743, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34825984

RESUMO

PURPOSE: Surgical site infection (SSI) frequently occurs in patients with head and neck cancer (HNC) after tumor resection and can lead to death in severe cases. Moreover, there is no definitive conclusion about the risk factors of SSI. Therefore, it is of great clinical significance to study the factors affecting the SSI. METHODS: The HNC patients included in this study were all from the Department of Oral and Maxillofacial Surgery of the Second Xiangya Hospital of Central South University (CSU), and these patients received surgical treatment in the department from January 2018 to December 2019. The cross tabulation with chi-squared testing and multivariate regression analysis were applied to determine the risk factors of SSI. To identify the key risk factors of SSI, the caret package was used to construct three different machine learning models to investigate important features involving 26 SSI-related risk factors. RESULTS: Participants were 632 HNC patients who underwent surgery in our department from January 2018 to December 2019. During the postoperative period, 82 patients suffered from SSI, and surgical site infection rate (SSIR) was about 12.97%. Multivariate logistic regression analysis shows that diabetes mellitus, primary tumor site (floor of mouth), preoperative radiotherapy, flap failure, and neck dissection (bilateral) are risk factors for SSI of HNC. Machine learning indicated that diabetes mellitus, primary tumor site (floor of mouth), and flap failure were consistently ranked the top three in the 26 SSI-related risk factors. CONCLUSION: Diabetes mellitus, primary tumor site (floor of mouth), flap failure, preoperative radiotherapy, and neck dissection (bilateral) are risk factors for SSI of HNC.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecção da Ferida Cirúrgica , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Esvaziamento Cervical , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia
7.
Nat Chem Biol ; 17(11): 1132-1138, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34475565

RESUMO

The RNA-guided CRISPR-associated (Cas) nucleases are versatile tools for genome editing in various organisms. The large sizes of the commonly used Cas9 and Cas12a nucleases restrict their flexibility in therapeutic applications that use the cargo-size-limited adeno-associated virus delivery vehicle. More compact systems would thus offer more therapeutic options and functionality for this field. Here, we report a miniature class 2 type V-F CRISPR-Cas genome-editing system from Acidibacillus sulfuroxidans (AsCas12f1, 422 amino acids). AsCas12f1 is an RNA-guided endonuclease that recognizes 5' T-rich protospacer adjacent motifs and creates staggered double-stranded breaks to target DNA. We show that AsCas12f1 functions as an effective genome-editing tool in both bacteria and human cells using various delivery methods, including plasmid, ribonucleoprotein and adeno-associated virus. The small size of AsCas12f1 offers advantages for cellular delivery, and characterizations of AsCas12f1 may facilitate engineering more compact genome-manipulation technologies.


Assuntos
Bacillales/química , Proteínas de Bactérias/genética , Proteínas Associadas a CRISPR/genética , Proteínas de Bactérias/metabolismo , Proteínas Associadas a CRISPR/metabolismo , Edição de Genes
8.
ACS Omega ; 6(34): 22383-22394, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34497927

RESUMO

CO2 reforming of methane was studied at medium temperature (700 °C) using a GSHV of 48,000 h-1 over nickel catalysts supported on ZrO2 promoted by alumina. The catalysts were prepared by a one-step synthesis method and characterized by BET, H2-TPR, XRD, XPS, TEM, Raman spectroscopy, and TGA. The NiO-10Al2O3-ZrO2 catalyst exhibited higher catalytic performance in comparison with the NiO-ZrO2 catalyst. The enhancement of catalytic activity in dry reforming could be associated with the alterations in surface properties due to Al promotion. First, the Al promoter could modify the structure of ZrO2, leading to an increase of its pore volume and pore diameter. Second, the NiO-10Al2O3-ZrO2 catalyst exhibited high resistance to sintering. Third, the NiO-10Al2O3-ZrO2 catalyst showed high suppression to the loss of nickel during a long-term catalytic test. Finally, the addition of Al could inhibit the reduction of ZrO2 during the reduction and reaction, endowing further the stability.

9.
Am J Pathol ; 191(9): 1638-1650, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34119472

RESUMO

Cullin (CUL) 4A and 4B ubiquitin ligases are often highly accumulated in human malignant neoplasms and are believed to possess oncogenic properties. However, the underlying mechanisms by which CUL4A and CUL4B promote pulmonary tumorigenesis remain largely elusive. This study reports that CUL4A and CUL4B are highly expressed in patients with non-small cell lung cancer (NSCLC), and their high expression is associated with disease progression, chemotherapy resistance, and poor survival in adenocarcinomas. Depletion of CUL4A (CUL4Ak/d) or CUL4B (CUL4Bk/d) leads to cell cycle arrest at G1 and loss of proliferation and viability of NSCLC cells in culture and in a lung cancer xenograft model, suggesting that CUL4A and 4B are oncoproteins required for tumor maintenance of certain NSCLCs. Mechanistically, increased accumulation of the cell cycle-dependent kinase inhibitor p21/Cip1/WAF1 was observed in lung cancer cells on CUL4 silencing. Knockdown of p21 rescued the G1 arrest of CUL4Ak/d or CUL4Bk/d NSCLC cells, and allowed proliferation to resume. These findings reveal that p21 is the primary downstream effector of lung adenocarcinoma dependence on CUL4, highlight the notion that not all substrates respond equally to abrogation of the CUL4 ubiquitin ligase in NSCLCs, and imply that CUL4Ahigh/CUL4Bhigh may serve as a prognostic marker and therapeutic target for patients with NSCLC.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Proteínas Culina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/patologia , Animais , Biomarcadores/metabolismo , Proliferação de Células , Sobrevivência Celular , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Xenoenxertos , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Prognóstico , Transdução de Sinais/fisiologia , Ubiquitina/metabolismo
10.
Angew Chem Int Ed Engl ; 60(31): 17164-17170, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34014019

RESUMO

The structural arrangement of amino acid residues in native enzymes underlies their remarkable catalytic properties, thus providing a notable point of reference for designing potent yet simple biomimetic catalysts. Herein, we describe a minimalistic approach to construct a dipeptide-based nano-superstructure with enzyme-like activity. The self-assembled biocatalyst comprises one peptide as a single building block, readily synthesized from histidine. Through coordination with zinc ion, the peptide self-assembly procedure allows the formation of supramolecular ß-sheet ordered nanocrystals, which can be used as basic units to further construct higher-order superstructure. As a result, remarkable hydrolysis activity and enduring stability are demonstrated. Our work exemplifies the use of a bioinspired supramolecular assembly approach to develop next-generation biocatalysts for biotechnological applications.


Assuntos
Nanopartículas/química , Peptídeos/química , Histidina/química , Hidrólise , Tamanho da Partícula , Peptídeos/síntese química
11.
mBio ; 12(2)2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879582

RESUMO

Base editing is a powerful genome editing approach that enables single-nucleotide changes without double-stranded DNA breaks (DSBs). However, off-target effects as well as other undesired editings at on-target sites remain obstacles for its application. Here, we report that bubble hairpin single guide RNAs (BH-sgRNAs), which contain a hairpin structure with a bubble region on the 5' end of the guide sequence, can be efficiently applied to both cytosine base editor (CBE) and adenine base editor (ABE) and significantly decrease off-target editing without sacrificing on-target editing efficiency. Meanwhile, such a design also improves the purity of C-to-T conversions induced by base editor 3 (BE3) at on-target sites. Our results present a distinctive and effective strategy to improve the specificity of base editing.IMPORTANCE Base editors are DSB-free genome editing tools and have been widely used in diverse living systems. However, it is reported that these tools can cause substantial off-target editings. To meet this challenge, we developed a new approach to improve the specificity of base editors by using hairpin sgRNAs with a bubble. Furthermore, our sgRNA design also dramatically reduced indels and unwanted base substitutions at on-target sites. We believe that the BH-sgRNA design is a significant improvement over existing sgRNAs of base editors, and our design promises to be adaptable to various base editors. We expect that it will make contributions to improving the safety of gene therapy.


Assuntos
Edição de Genes/métodos , RNA Guia de Cinetoplastídeos/genética , Adenina , Sistemas CRISPR-Cas , Citosina , Células HEK293 , Humanos , Mutação
12.
BMC Cancer ; 21(1): 256, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750338

RESUMO

BACKGROUND: Head and neck cancers are aggressive cancers, most clinical studies focused on the prognosis of patients with head and neck cancer. However, perioperative mortality was rarely mentioned. METHODS: A retrospective analysis was performed using all head and neck cancer patients admitting in the Department of Oral and Maxillofacial Surgery of the Second Xiangya Hospital, Central South University from January 2010 to December 2019. The analysis of overall survival and progression-free survival were performed using the Kaplan-Meier method, and cross tabulation with chi-squared testing was applied to analyze the difference in parameters between groups. RESULTS: From January 2010 to December 2019, a total of 6576 patients with head and neck cancers were admitted to our department and 7 died in the hospital, all of whom were middle-aged and elderly patients including 6 males and 1 female. The perioperative mortality rate (POMR) was about 1‰. The causes of death included acute heart failure, rupture of large blood vessels in the neck, hypoxic ischemic encephalopathy due to asphyxia, respiratory failure and cardiopulmonary arrest. CONCLUSION: Preoperative radiotherapy, previous chemotherapy, hypertension, diabetes, advanced clinical stage and postoperative infection are risk factors for perioperative mortality of head and neck cancer.


Assuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Adulto , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Perioperatório , Estudos Retrospectivos
13.
Gynecol Oncol Rep ; 35: 100701, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33537390

RESUMO

•Overall prognosis of uterine leiomyosarcoma (ULMS) is poor with a low 5-year survival rate.•Microsatellite instability (MSI)-high ULMS is not well documented in current literature.•Immune checkpoint inhibitors such as pembrolizumab have been shown to have good efficacy in treating MSI-high solid tumors.•Targeting MSI-high ULMS with pembrolizumab can potentially maintain a patient's quality of life and extend overall survival.

14.
Dig Liver Dis ; 52(7): 773-779, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31959478

RESUMO

Increasing evidence shows that aberrant lncRNAs expression contributes to the progression of gastric cancer (GC). The role of the novel lncRNA OIP5-AS1 and its underlying mechanisms in the growth of GC is largely unknown. Here we demonstrate for the first time that OIP5-AS1 expression was up-regulated in GC tissues and cell lines, which significantly correlated with unfavorable clinical characteristics and shorter survival. The results of in vitro and in vivo gain- and loss-of-function experiments indicate that OIP5-AS1 promoted cell proliferation and colony formation while inhibiting apoptosis of GC cells. OIP5-AS1 functioned as an endogenous sponge for miR-367-3p in GC cells. Restoration of miR-367-3p expression abolished the biological effects of OIP5-AS1 on GC cells. Moreover, we show that HMGA2 was a downstream target of miR-367-3p and mediated the effects of OIP5-AS1 on GC cells. OIP5-AS1 regulated the activities of the PI3K/AKT and Wnt/ß-catenin pathways through HMGA2. In conclusion, OIP5-AS1 functions as an oncogenic lncRNA that promotes the progression of GC and may serve as a therapeutic target for managing GC.


Assuntos
Proteína HMGA2/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Animais , Apoptose , Carcinogênese/genética , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
15.
BMC Oral Health ; 20(1): 5, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906928

RESUMO

BACKGROUND: Head and neck Synovial sarcoma (SS) accounts for 3-10% of all total body SS. It is rare to find it in the oral cavity, especially on the floor of the mouth. CASE PRESENTATION: We present a 44-year-old Chinese male, who had been misdiagnosed as fibroadenoma, with a swelling on the right submandibular region for more than 3 months. The radiology examinations and the pathology results indicate the diagnosis of SS of the floor of the mouth. The patient only had a surgical operation, without radiotherapy and chemotherapy. At the first follow-up, the patient exhibited no clinical or radiographic complications, and the patient was asymptomatic on subsequent visits. CONCLUSIONS: Misdiagnosis results the delay of diagnosis and treatment of SS. Immunohistological analysis might be the most important tool to confirm the diagnosis of SS.


Assuntos
Neoplasias Bucais/patologia , Sarcoma Sinovial/patologia , Adulto , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Soalho Bucal/patologia , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sarcoma Sinovial/cirurgia , Resultado do Tratamento
16.
Medicine (Baltimore) ; 98(31): e16625, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374029

RESUMO

Cullin proteins couple with RING-finger proteins, adaptor proteins and substrate recognition receptors to form E3 ubiquitin ligases for recognizing numerous substrates and participating in a variety of cellular processes, especially in genome stability and tumorigenesis. However, the prognostic values of Cullins in breast cancer remain elusive.A "Kaplan-Meier plotter" (KM plotter) online survival analysis tool was used to evaluate the association of individual Cullin members' mRNA expression with overall survival (OS) in breast cancer patients.Our results revealed that elevated mRNA expression of CUL4A and PARC were significantly associated with poor OS for breast cancer patients. While high mRNA expression of CUL2, CUL4B, and CUL5 were correlated with better survival for breast cancers.The associated results suggested that some Cullin members could serve as new predictive prognostic indicators for breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Proteínas Culina/biossíntese , RNA Mensageiro/biossíntese , Neoplasias da Mama/patologia , Proteínas de Transporte/biossíntese , Humanos , Estimativa de Kaplan-Meier , Gradação de Tumores , Transferases
17.
J Cell Biochem ; 119(11): 8862-8871, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30125971

RESUMO

Oral lichen planus (OLP) is a severe T cell-mediated disorder of the mucosa, which causes chronic inflammation. Forkhead box P3 (Foxp3) regulates the immune response and plays an important role in immunological diseases. The current study aimed to determine the role of Foxp3 and microRNA (miR)-146a in OLP. Western blot analysis and a quantitative real-time polymerase chain reaction assay showed that the expression of Foxp3 and miR-146a was upregulated in OLP tissues and in lipopolysaccharide (LPS)-incubated HaCaT cells, compared with controls. Foxp3 inhibition significantly decreased miR-146a expression, ameliorated LPS stimulation by decreased cell proliferation, and apoptosis in LPS-incubated HaCaT cells as compared with the LPS group. Cotransfection of Foxp3 small interfering RNA and miR-146a mimics elevated cell proliferation and apoptosis compared with the Foxp3 small interfering RNA group. In addition, miR-146a overexpression upregulated, whereas miR-146a inhibition downregulated, the proliferation and apoptosis of LPS-incubated HaCaT cells. The target gene of miR--146a, tumor necrosis factor receptor-associated factor 6 (TRAF6), was predicted by bioinformatics software and identified by the luciferase reporter assay. Furthermore, Foxp3/miR-146a elevated T regulatory cells and regulated TRAF6 expression in CD4+ T cells that were isolated from peripheral blood of patients with OLP. In conclusion, our study suggests that Foxp3 and miR-146a regulate the progression of OLP by negatively regulating TRAF6, which may provide a promising therapeutic target for OLP treatment.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Líquen Plano Bucal/sangue , Líquen Plano Bucal/patologia , MicroRNAs/metabolismo , Regiões 3' não Traduzidas/genética , Análise de Variância , Apoptose , Biópsia , Linhagem Celular , Proliferação de Células , Biologia Computacional/métodos , Progressão da Doença , Fatores de Transcrição Forkhead/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Queratinócitos/metabolismo , Lipopolissacarídeos/farmacologia , MicroRNAs/química , MicroRNAs/genética , Mimetismo Molecular , Linfócitos T Reguladores/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Transfecção , Regulação para Cima
18.
World Neurosurg ; 119: e145-e158, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30053564

RESUMO

OBJECTIVE: This study aimed to clarify the relationship between histone deacetylase 3 (HDAC3) expression and the prognosis as well as the grade of patients with glioma. METHODS: The quantitative real-time polymerase chain reaction was profiled to examine the HDAC3 expression in glioma and normal glial cell lines. An Oncomine database analysis and prognosis analysis were performed. The correlation between World Health Organization (WHO) grade and HDAC3 was analyzed by Spearman rank correlation test. A meta-analysis was performed to confirm the conclusion. RESULTS: HDAC3 RNA overexpression in glioma cell lines was detected (P < 0.05). Four data sets were screened from the Oncomine database and showed that the expression level of HDAC3 was consistently higher in glioma than in normal tissue (P < 0.001). The prognostic analysis of 325 glioma samples from the Chinese Glioma Genome Atlas showed that patients with low HDAC3 expression had significantly better overall survival (OS) and progression-free survival (PFS) than did patients with high HDAC3 expression [hazard ratio [HR], 1.992; 95% confidence interval [CI], 1.490-2.662; P < 0.0001 and HR, 1.874; 95% CI, 1.412-2.487; P < 0.0001, respectively]. Both the WHO grade III group and the WHO grade IV group expressed significantly higher messenger RNA (mRNA) level than did the WHO grade II group (P < 0.05). Four cohort studies consisting of 490 patients were included in the meta-analysis. The pooled data of subgroup analysis showed significantly longer OS in low HDAC3 mRNA level [HR, 3.38; 95% CI, 1.80-6.37; P = 0.0002]. CONCLUSIONS: HDAC3 mRNA was expressed more in glioma than in the normal glial cell line. Low HDAC3 mRNA expression levels predicted better OS. HDAC3 expression could be a biomarker to discriminate glioma grade.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioma/diagnóstico , Glioma/metabolismo , Histona Desacetilases/metabolismo , Transcriptoma , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Feminino , Glioma/mortalidade , Glioma/terapia , Histona Desacetilases/genética , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo , Análise de Sobrevida
19.
J Cancer ; 9(13): 2317-2326, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30026827

RESUMO

MicroRNAs (miRNAs) are involved in cancer genesis and progression via acting as tumor suppressors or oncogenes. Previous studies report that miR-1296 shows upregulation in both colorectal cancer (CRC) tissues and plasma samples. However, the accurate clinical significance of miR-1296 and its role in CRC have not been well investigated. The aim of the present study was to disclose the aberrant expression, clinical significance, and the relevant biological function of miR-1296 in CRC. We found a marked upregulation of miR-1296 expression in CRC tissues compared to tumor-adjacent tissues. MiR-1296 overexpression was detected in five CRC cell lines (HCT116, Caco2, HT29, SW620 and SW480). High miR-1296 level was remarkably correlated with tumor size (>5cm), lymph node metastasis and TNM stage (III+IV). Notably. High miR-1296 expression was identified as a predictive factor for poor prognosis of CRC patients by survival analysis. MiR-1296 knockdown inhibited proliferation, migration, invasion capacities of HCT116 and SW480 cells in vitro. Moreover, miR-1296 silencing restrained the growth of CRC cells in vivo. Splicing factor proline and glutamine rich (SFPQ), a novel RNA binding protein, was identified as a direct target gene of miR-1296 in CRC. Downregulation of SFPQ expression was inversely associated with miR-1296 expression in CRC tissues. The Cancer Genome Atlas (TCGA) data revealed the prognostic value of dysregulated SFPQ in CRC patients. Interestingly, our findings established that the oncogenic role of miR-1296 was at least partially mediated by SFPQ in CRC cells. Collectively, these data indicate that miR-1296 accelerates CRC progression possibly by targeting SFPQ and may serve as a potential predictive factor and therapeutic target for CRC.

20.
Biomed Pharmacother ; 103: 1369-1375, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29864920

RESUMO

Transcription factor forkhead box D1 (FOXD1), a member of forkhead box family, has been recognized as a caner-related gene. Aberrant expression of FOXD1 is observed in glioma, lung cancer and breast cancer. However, the clinical significance of FOXD1 and its role in colorectal cancer (CRC) are unknown. Here, we found that FOXD1 displayed a higher expression in CRC tissues compared to tumor-adjacent tissues. Upregulation of FOXD1 was further confirmed in CRC tissues compared to normal tissues based on data from three GSE cohorts. Our clinical data indicated that high FOXD1 level was associated with tumor size (≥5 cm) and TNM tumor stage (III + IV). Moreover, both our data and TCGA data found that high expression of FOXD1 predicted poor prognosis of CRC patients. Next, we revealed that FOXD1 knockdown suppressed proliferation, cell cycle progression and induced apoptosis of SW480 cells in vitro. In accordance, FOXD1 overexpression promoted proliferation and reduced apoptosis of HT29 cells. Interestingly, polo-like kinase 2 (Plk2) expression was elevated and it positively correlated with FOXD1 expression in CRC tissues. FOXD1 promoted the expression of Plk2 mRNA and protein in CRC cells. Notably, Plk2 restoration abolished the effect of FOXD1 knockdown on proliferation and apoptosis of SW480 cells. Plk2 knockdown resulted in decreased proliferation and increased apoptosis of FOXD1-overexpressing HT29 cells. Altogether, we demonstrate for the first time that FOXD1 functions as an oncoprotein and a potential prognostic biomarker in CRC.


Assuntos
Apoptose , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fatores de Transcrição Forkhead/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Prognóstico , Regulação para Cima/genética
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