Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Exp Clin Cancer Res ; 39(1): 30, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32028981

RESUMO

BACKGROUND: BRD7 is a tumor suppressor known to inhibit cell proliferation and cell cycle progression and initiate apoptosis in breast cancer. However, the function and underlying molecular events of BRD7 in tumor invasion and metastasis in breast cancer are not fully understood. METHODS: BRD7 expression was assessed in two stable cell lines MDA231 and MCF7 with BRD7 overexpression and one stable cell line MDA231 with BRD7 interference using qRT-PCR and western blotting. CCK8 assay was used to examine the proliferation ability of MDA231 and MCF7 cells. Scratch wound healing assay was used to evaluate cell migration in MDA231 and MCF7 cells. Both Matrigel and three-dimensional invasion assays were performed to investigate the cell invasion ability after BRD7 overexpression or silencing or YB1 restoration in MDA231 and MCF7 cells. The potential interacting proteins of BRD7 were screened using co-immunoprecipitation combined with mass spectrometry and verified by co-immunoprecipitation in HEK293T cells. Additionally, we confirmed the specific binding region between BRD7 and YB1 in HEK293T cells by constructing a series of deletion mutants of BRD7 and YB1 respectively. Finally, xenograft and metastatic mouse models using MDA231 cells were established to confirm the effect of BRD7 on tumor growth and metastasis. RESULTS: Here, the results of a series of assays in vitro indicated that BRD7 has the ability to inhibit the mobility, migration and invasion of breast cancer cells. In addition, YB1 was identified as a novel interacting protein of BRD7, and BRD7 was found to associate with the C-terminus of YB1 via its N-terminus. BRD7 decreases the expression of YB1 through negatively regulating YB1 phosphorylation at Ser102, thereby promoting its proteasomal degradation. Furthermore, gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT) is the common change occurring with altered expression of either BRD7 or YB1 and that BRD7 represses mesenchymal genes and activates epithelial genes. Moreover, restoring the expression of YB1 antagonized the inhibitory effect of BRD7 on tumorigenicity, EMT, invasiveness and metastasis through a series of in vitro and in vivo experiments. Additionally, BRD7 expression was negatively correlated with the level of YB1 in breast cancer patients. The combination of low BRD7 and high YB1 expression was significantly associated with poor prognosis, distant metastasis and advanced TNM stage. CONCLUSIONS: Collectively, these findings uncover that BRD7 blocks tumor growth, migration and metastasis by negatively regulating YB1-induced EMT, providing new insights into the mechanism by which BRD7 contributes to the progression and metastasis of breast cancer.

2.
Biochem Cell Biol ; 97(6): 702-708, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31770017

RESUMO

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3ß (GSK-3ß), to evaluate the role of the Wnt-ß-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood-brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of ß-catenin and downstream proteins while suppressing the expression of GSK-3ß. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt-ß-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.

3.
Front Oncol ; 9: 683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403034

RESUMO

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare type of lymphoma with a high incidence in elderly patients, poor drug response, and unfavorable prognosis. Despite advances in genomic profiling and precision medicine in DLBCL, EBV+ DLBCL remain poorly characterized and understood. We include 236 DLBCL patients for EBV-encoded mRNA (EBER) in situ hybridization detection and analyzed 9 EBV+ and 6 EBV negative cases by next-generation sequencing (NGS). We then performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to analyze chromosome rearrangements and gene expressions in 22 EBV+ and 30 EBV negative cases. The EBER results showed a 9.3% (22/236) positive rate. The NGS results revealed recurrent alterations in MYC and RHOA, components of apoptosis and NF-κB pathways. The most frequently mutated genes in EBV+ DLBCL were MYC (3/9; 33.3%), RHOA (3/9; 33.3%), PIM1 (2/9; 22.2%), MEF2B (2/9; 22.2%), MYD88 (2/9; 22.2%), and CD79B (2/9; 22.2%) compared with KMT2D (4/6; 66.7%), CREBBP (3/6; 50.0%), PIM1 (2/6; 33.3%), TNFAIP3 (2/6; 33.3%), and BCL2 (2/6; 33.3%) in EBV-negative DLBCL. MYC and KMT2D alterations stood out the most differently mutated genes between the two groups. FISH detection displayed a lower rearrangement rate in EBV+ cohort. Furthermore, KMT2D expression was highly expressed and associated with poor survival in both cohorts. MYC was only overexpressed and related to an inferior prognosis in the EBV+ DLBCL cohort. In summary, we depicted a distinct mutation profile for EBV+ and EBV-negative DLBCL and validated the differential expression of KMT2D and MYC with potential prognostic influence, thereby providing new perspectives into the pathogenesis and precision medicine of DLBCL.

4.
J Cell Mol Med ; 23(9): 6060-6071, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211507

RESUMO

The integrated stress response (ISR) is critical for cancer cell survival during stress stimuli and has been implicated in the resistance to cancer therapeutics, in which the mechanism, however, is poorly understood. Here, we showed that paclitaxel, the major chemotherapy drug for breast cancer, induced ISR and phosphorylated ser51 residue of EIF2S1 by EIF2AK3 and EIF2AK4. When exposed to paclitaxel, cancer cells activated the EIF2AK3/EIF2AK4-pEIF2S1-ATF4 axis and maintained redox homoeostasis by inducing expression of the major antioxidant enzymes HMOX1, SHMT2 and SLC7A11. Paclitaxel-mediated cell death was significantly increased following loss of ISR or ATF4 expression. This sensitizing effect could be partially rescued by Trolox, a ROS scavenger. We demonstrated that the alternative initiation factor EIF2A was essential for cancer cell survival after paclitaxel-mediated ISR both in vitro and in vivo. Moreover, patients with breast cancer exhibited higher ISR after chemotherapy, and the elevated mRNA levels of HMOX1, SHMT2 and EIF2A were correlated with poor prognosis. Collectively, our findings reveal a novel mechanism for paclitaxel resistance and suggest that targeting EIF2A combined with ISR agonist may be a potential treatment regimen to overcome drug resistance for breast cancer.

5.
Front Oncol ; 9: 369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31143705

RESUMO

Intrahepatic cholangiocarcinoma (ICC) ranks as the second most malignant type of primary liver cancer with a high degree of incidence and a very poor prognosis. Fat mass and obesity-associated protein (FTO) functions as an eraser of the RNA m6A modification, but its roles in ICC tumorigenesis and development remain unknown. We showed here that the protein level of FTO was downregulated in clinical ICC samples and cell lines and that FTO expression was inversely correlated with the expression of CA19-9 and micro-vessel density (MVD). A Kaplan-Meier survival analysis showed that a low expression of FTO predicted poor prognosis in ICC. in vitro, decreased endogenous expression of FTO obviously reduced apoptosis of ICC cells. Moreover, FTO suppressed the anchorage-independent growth and mobility of ICC cells. Through mining the database, FTO was found to regulate the integrin signaling pathway, inflammation signaling pathway, epidermal growth factor receptor (EGFR) signaling pathway, angiogenesis, and the pyrimidine metabolism pathway. RNA decay assay showed that oncogene TEAD2 mRNA stability was impaired by FTO. In addition, the overexpression of FTO suppressed tumor growth in vivo. In conclusion, our study demonstrated the critical roles of FTO in ICC.

6.
Redox Biol ; 24: 101189, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30986607

RESUMO

Radiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative analysis of RT-treated recurrent tumors versus primary counterparts in GBM patients, RT-treated orthotopic GBM tumors xenografts versus untreated tumors and radioresistant GBM cells versus wild type cells. The results reveal that activation of STAT3, a well-defined redox-sensitive transcriptional factor, is causally linked with GBM adaptive radioresistance. Database analysis also agrees with the worse prognosis in GBM patients due to the STAT3 expression-associated low RT responsiveness. However, although the radioresistant GBM cells can be resensitized by inhibition of STAT3, a fraction of radioresistant cells can still survive the RT combined with STAT3 inhibition or CRISPR/Cas9-mediated STAT3 knockout. A complementally enhanced activation of ERK1/2 by STAT3 inhibition is identified responsible for the survival of the remaining resistant tumor cells. Dual inhibition of ERK1/2 and STAT3 remarkably eliminates resistant GBM cells and inhibits tumor regrowth. These findings demonstrate a previously unknown feature ofSTAT3-mediated ERK1/2 regulation and an effective combination of two targets in resensitizing GBM to RT.

7.
Sci China Life Sci ; 62(5): 640-647, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30900169

RESUMO

Cancer is the leading cause of human deaths in the world and produces serious economic burdens. On September 12, 2018, the academic journal A Cancer Journal for Clinicians published an article about the latest statistics of cancers worldwide, which provided a status report on the global burden of 36 cancers in 185 countries worldwide. Cancer has also become a serious public health problem in China and caused more and more attention of the government and people in recent years. This review analyzes the incidence, mortality and prevalent trend of cancers in China, discusses the reasons behind this status, and reviews the potential countermeasures for cancer prevention and control in China.

8.
Curr Probl Cancer ; 43(5): 429-437, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30678988

RESUMO

Yes-associated protein (YAP) protein acts as tumorigenic factor in many solid tumors, but the situation in breast cancer is under debate. Here, we would analyze its status in breast cancer. YAP expression in the 110 primary breast cancer and their paired local recurrent tumors was investigated. Clinicopathologic data for age, histologic grading, hormone status, lymph nodes and HER2 status were also gathered and analyzed. 46.4% (51/110) primary breast cancer tissues were positive for total YAP expression which was significantly higher than that in the recurrent tissues (10.9%; P < 0.05). The expression of total YAP protein in the primary breast cancer tissues was positively associated with the tumor size, especially in triple negative breast cancer (TNBC) subtype (P < 0.05). Higher total or nuclear YAP expression in the primary tumor was correlated with poor disease-free survival among patients with TNBC (P < 0.05). In the multivariate models, nuclear YAP expression was an independently prognostic factor in TNBC. High total or nuclear YAP expression predicts poor prognosis among patients with TNBC. It might be a therapeutic target for TNBC in the future.

9.
Biochim Biophys Acta Mol Basis Dis ; 1865(6): 1201-1213, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30659926

RESUMO

Viral noncoding RNAs (Epstein-Barr virus-encoded RNAs, EBERs) are believed to play a critical role in the progression of lymphoma and nasopharyngeal carcinoma (NPC). However, the accurate mechanisms accounting for their oncogenic function have not been elucidated, especially in terms of interaction between tumor cells and mesenchymal cells. Here, we report that, in addition to NPC cells, EBERs are also found in endothelial cells in Epstein-Barr virus (EBV)-infected NPC parenchymal tissues, which implicates NPC-derived extracellular vesicles (EVs) in transmitting EBERs to endothelial cells. In support of this hypothesis, we first ascertained if EBERs could be transferred to endothelial cells via EVs isolated from NPC culture supernatant. Then, we clarified that EVs-derived EBERs could promote angiogenesis through stimulation of VCAM-1 expression. Finally, we explored the involvement of EBER recognition by TLR3 and RIG-I in NPC angiogenesis. Our observations collectively illustrate the significance and mechanism of EVs-derived EBERs in angiogenesis and underlie the interaction mechanisms between EBV-infected NPC cells and the tumor microenvironment.

10.
Hum Pathol ; 86: 38-48, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30496796

RESUMO

Pleomorphic xanthoastrocytoma (PXA) is a rare central nervous system tumor occurring mostly in children and young adults. Next-generation sequencing of 295 cancer-related genes was used to investigate the molecular profiles of 13 cases of PXA. We found that BRAF V600E (5/13; 38%), FANCA/D2/I/M (5/13; 38%), PRKDC (4/13; 31%), NF1 (3/13; 23%), and NOTCH2/3/4 (3/13; 23%) alterations were the most frequent somatic gene mutations. However, neither PTEN nor EGFR mutation, which is frequently present in glioblastoma, was detected. The KRAS mutation in PXA is reported for the first time in these tumors. Microsatellite stability was present in all cases. Because mutations of FANCA and BRAF and copy number variations of CDKN2A/B are more frequent in PXA than in glioblastoma, they might be used to distinguish the 2 tumors. The MAPK pathway is involved in the pathogenesis of PXA and may be an effective target for treatment.


Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Mutação , Adolescente , Adulto , Astrocitoma/metabolismo , Astrocitoma/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação A da Anemia de Fanconi/metabolismo , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
11.
Neoplasia ; 20(10): 1059-1069, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30227305

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma. The treatment of PCNSL is comprehensive, combining surgery, radiotherapy, and chemotherapy. However, the outcome is poor because of its high invasiveness and rate of recurrence. We analyzed 22 cases of PCNSL using next-generation sequencing (NGS) to detect 64 candidate genes. We used immunohistochemical methods to analyze gene expression in 57 PCNSL samples. NGS showed that recurrent mutations in KMT2D and CD79B, components of the NF-κB pathway, accounted for 65% of total mutations in PCNSL samples. The most frequent mutated gene was PIM1 (77.27%, 17/22), followed by MYD88 (63.64%, 14/22), CD79B (69.09%, 13/22), and KMT2D (50.00%, 11/22). Mutations of the CD79B gene were associated with an inferior progression-free survival (PFS), and GNA13 gene mutations were associated with a shorter PFS and overall survival (OS) in PCNSL patients (P < .05). PIM1 and MYD88 were highly expressed in PCNSL patients and were related to their OS time. MYD88 overexpression might be an independent and poor prognostic predictor of OS time. In summary, we identified highly recurrent genetic lesions in CD79B and KMT2D, components of the NF-κB pathway, in PCNSL and validated the expression of PIM1 and MYD88 related to poor survival, thereby providing novel insights into the pathogenesis and precision medicine of PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Regulação Neoplásica da Expressão Gênica , Linfoma/genética , Mutação , Adolescente , Adulto , Idoso , Antígenos CD79/genética , Neoplasias do Sistema Nervoso Central/mortalidade , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Proteínas de Neoplasias/genética , Prognóstico , Proteínas Proto-Oncogênicas c-pim-1/genética , Proteínas Proto-Oncogênicas c-pim-1/metabolismo
12.
Cell Death Dis ; 8(3): e2659, 2017 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-28277541

RESUMO

Paclitaxel is clinically used as a first-line chemotherapeutic regimen for several cancer types, including head and neck cancers. However, acquired drug resistance results in the failure of therapy, metastasis and relapse. The drug efflux mediated by ATP-binding cassette (ABC) transporters and the survival signals activated by forkhead box (FOX) molecules are critical in the development of paclitaxel drug resistance. Whether FOX molecules promote paclitaxel resistance through drug efflux remains unknown. In this study, we developed several types of paclitaxel-resistant (TR) nasopharyngeal carcinoma (NPC) cells. These TR NPC cells acquired cancer stem cell (CSC) phenotypes and underwent epithelial to mesenchymal transition (EMT), and developed multidrug resistance. TR cells exhibited stronger drug efflux than parental NPC cells, leading to the reduction of intracellular drug concentrations and drug insensitivity. After screening the gene expression of ABC transporters and FOX molecules, we found that FOXM1 and ABCC5 were consistently overexpressed in the TR NPC cells and in patient tumor tissues. Further studies demonstrated that FOXM1 regulated abcc5 gene transcription by binding to the FHK consensus motifs at the promoter. The depletion of FOXM1 or ABCC5 with siRNA significantly blocked drug efflux and increased the intracellular concentrations of paclitaxel, thereby promoting paclitaxel-induced cell death. Siomycin A, a FOXM1 inhibitor, significantly enhanced in vitro cell killing by paclitaxel in drug-resistant NPC cells. This study is the first to identify the roles of FOXM1 in drug efflux and paclitaxel resistance by regulating the gene transcription of abcc5, one of the ABC transporters. Small molecular inhibitors of FOXM1 or ABCC5 have the potential to overcome paclitaxel chemoresistance in NPC patients.


Assuntos
Carcinoma/tratamento farmacológico , Proteína Forkhead Box M1/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Paclitaxel/administração & dosagem , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais
13.
Acta Otolaryngol ; 137(6): 662-667, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28084179

RESUMO

CONCLUSION: In patients with nasopharyngeal carcinoma (NPC), PKCα is linked to local advancement and plays dual roles in tumorigenesis. Moreover, positive PKCα is associated with 2-year overall survival of NPC. OBJECTIVE: This study seeks to investigate the role of PKCα to identify different sub-types in NPC. METHODS: PKCα expression levels were detected in a collection of NPC samples. CT and MRI scans of the corresponding patients were used to assess adjacent tissue invasion and lymph node metastasis. The correlation of tumour invasion and PKCα levels was evaluated by statistical analysis. The correlation between expression level of PKCα and 2-year overall survival was analysed by the Kaplan-Meier curves. Moreover, a multivariate Cox proportional hazard regression analysis was used to identify the independent prognostic factors for NPC. RESULTS: PKCα is linked to the invasion of adjacent tissues, especially in the skull base. However, down-regulation of PKCα is a risk factor for regional lymph node metastasis. The 2-year overall survival of the PKCα negative group is better than that of the PKCα positive group (PKCα negative group 100%, PKCα positive group 88.5%, p = 0.034). Based on the multivariate Cox proportional hazard regression analysis, age was identified as a risk factor.


Assuntos
Carcinoma/enzimologia , Neoplasias Nasofaríngeas/enzimologia , Proteína Quinase C-alfa/metabolismo , Adulto , Idoso , Carcinoma/mortalidade , Carcinoma/patologia , China/epidemiologia , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica , Adulto Jovem
14.
Oncotarget ; 6(27): 24291-303, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26172457

RESUMO

Pathogen-induced inflammation has been one of the intensive research areas in carcinogenesis. EBV encoded RNAs (EBERs) have been suggested to play roles in anti-apoptosis and growth-promotion in lymphoid and immune disorders. However, pathological roles of EBERs in solid tumors of epithelia origin remain to be elucidated. Given their characteristic dsRNA structures, recent studies provided evidences for the activation of some pattern recognition receptors (PRR) by EBERs, which is fundamental in the process of pathogenesis. Here, we show that EBERs induce inflammatory response in nasopharyngeal carcinoma (NPC) cells through Toll-like receptor 3 (TLR3), mainly featured by high level of TNFα production. Interestingly, EBERs and EBV latent membrane protein 1 (LMP1) form a positive regulatory loop with NF-κB as a key node that amplifies the inflammatory signals in EBV infected epithelial cells. We demonstrate in vivo that EBERs can interact with TLR3 and induce tumor cells to produce cytokines in B16 synergetic tumor and human NPC xenograft models, in which macrophages are recruited and activated, leading to a favorable microenvironment for solid tumor growth. Lastly, we verify a positive association between EBER and TNFα levels in NPC clinical samples and the combination of EBER and TNFα expressions provides a predictor of poor survival of NPC patients. In conclusion, EBERs play a pivotal role in inflammation-to-oncogenesis transition in NPC development.


Assuntos
Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/metabolismo , RNA Viral/metabolismo , Receptor 3 Toll-Like/metabolismo , Animais , Apoptose , Carcinoma , Adesão Celular , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Infecções por Vírus Epstein-Barr/metabolismo , Feminino , Regulação Viral da Expressão Gênica , Humanos , Inflamação , Macrófagos/metabolismo , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo , Transplante de Neoplasias , RNA de Cadeia Dupla/metabolismo , Transdução de Sinais , Resultado do Tratamento , Células U937 , Proteínas da Matriz Viral/metabolismo
15.
Cancer Lett ; 361(1): 67-74, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-25721089

RESUMO

EBERs (EBER1 and EBER2) are suggested to be involved in cellular transformation and tumor growth. Cytoplasmic pattern recognition receptor-RIG-I, which is characterized by the recognition of viral dsRNAs, could efficiently trigger the downstream pathways of innate immunity. Although some previous reports have shown that EBERs and RIG-I associate with hematological malignancies, the role of EBERs-RIG-I signaling in solid tumors remains to be clarified. Here we demonstrate that EBER mediation of the inflammatory response via RIG-I contributes to NPC development in vitro and in vivo. We first verified that the expression level of RIG-I was associated with EBER transcription in a dose-dependent manner in NPC cells and specimens from NPC patients. Furthermore, pro-inflammatory cytokine transcription and release were sharply reduced after RIG-I knockdown compared with the control shRNA group in the presence of EBERs, accompanied by an attenuation of the NF-κB and MAPK signaling pathways. Consequently, the tumor burden was greatly alleviated in the RIG-I knockdown group in a xenograft model. In addition, macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein (MCP-1), which promote the maturation and attraction of tumor-associated macrophages, were stimulated upon the introduction of EBERs, and this upregulation conceivably led to the tumor-promoting subset transition of the macrophages. Taken together, our results reveal that EBERs could promote NPC progression through RIG-I-mediated cancer-related inflammation.


Assuntos
RNA Helicases DEAD-box/metabolismo , Inflamação/imunologia , Fator Regulador 3 de Interferon/metabolismo , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , RNA Viral/metabolismo , Animais , Western Blotting , Carcinoma , Diferenciação Celular , Técnicas de Cocultura , Citocinas/genética , Citocinas/metabolismo , Proteína DEAD-box 58 , RNA Helicases DEAD-box/antagonistas & inibidores , RNA Helicases DEAD-box/genética , Progressão da Doença , Feminino , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/análise , Fator Regulador 3 de Interferon/genética , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/genética , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , RNA Viral/antagonistas & inibidores , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Craniofac Surg ; 24(6): 2098-102, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24220415

RESUMO

BACKGROUND: The anterior clinoid process (ACP) is located close to the optic nerve, internal carotid artery, ophthalmic artery, and can be easily injured in an ACP-related surgery. An anatomical study clearly defining the ACP is of great importance. In addition, computed tomographic (CT) images may be a new tool for the anatomical analysis of ACP compared with the use of a cadaver and skull study, and more data related to ACP can be measured by CT images. PURPOSE: We studied the anatomical structure of ACP and the structures surrounding it to provide information to surgeons for ACP-related surgery. METHODS: Computed tomography angiographic images of 102 individuals were reviewed. The measurement was performed on coronal, sagittal, and axis planes after multiplanar reformation. The length of ACP and the distance between apex of ACP and sagittal midline were measured in the axial plane; the classification of ACP and the occurrence rate of bone bridge were also viewed in axial plane. The thickness of ACP was measured in sagittal plane. RESULT: In Chinese population, 12.3% of the ACP is gasified, and the pneumatization of ACP has a relationship with the pneumatization of sphenoid sinus. The length and thickness of ACP are similar to that in previous studies in cadaver. The apex of ACP is relatively stationary to the C3 and C4 segments of the internal carotid artery. The occurrence rate of anterior and middle clinoid bone bridge was 7.8%; the occurrence rate of anterior and posterior clinoid bone bridge was 9.3%. CONCLUSIONS: The anatomical structure of ACP can be studied effectively in CT images. Recognizing the anatomical characteristics of the ACP and optic strut is important in decreasing the incidence of surgical complications of an anterior clinoidectomy and in the proper intraoperative management to prevent these complications.


Assuntos
Osso Esfenoide/diagnóstico por imagem , Adulto , Idoso , Angiografia/métodos , Artéria Carótida Interna/diagnóstico por imagem , Cefalometria/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Artéria Oftálmica/diagnóstico por imagem , Nervo Óptico/diagnóstico por imagem , Osso Esfenoide/anatomia & histologia , Seio Esfenoidal/anatomia & histologia , Seio Esfenoidal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA