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Multifunctional vertically aligned nanocomposite (VAN) thin films exhibit considerable potential in diverse fields. Here, a BaTiO3-FeCoNi alloy (BTO-FCN) system featuring an ultrathin ternary FCN alloy nanopillar array embedded in the BTO matrix has been developed with tailorable nanopillar size and interpillar distance. The magnetic alloy nanopillars combined with a ferroelectric oxide matrix present intriguing multifunctionality and coupling properties. The room-temperature magnetic response proves the soft magnet nature of the BTO-FCN films with magnetic anisotropy has been demonstrated. Furthermore, the anisotropic nature of the dielectric-metal alloy VAN renders it an ideal candidate for hyperbolic metamaterial (HMM), and the epsilon-near-zero (ENZ) wavelength, where the real part of permittivity (ε') turns to negative, can be tailored from â¼700 nm to â¼1050 nm. Lastly, room-temperature multiferroicity has been demonstrated via interfacial coupling between the magnetic nanopillars and ferroelectric matrix.
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Filamentary-type resistive switching devices, such as conductive bridge random-access memory and valence change memory, have diverse applications in memory and neuromorphic computing. However, the randomness in filament formation poses challenges to device reliability and uniformity. To overcome this issue, various defect engineering methods have been explored, including doping, metal nanoparticle embedding, and extended defect utilization. In this study, we present a simple and effective approach using self-assembled uniform Au nanoelectrodes to controll filament formation in HfO2 resistive switching devices. By concentrating the electric field near the Au nanoelectrodes within the BaTiO3 matrix, we significantly enhanced the device stability and reduced the threshold voltage by up to 45% in HfO2-based artificial neurons compared to the control devices. The threshold voltage reduction is attributed to the uniformly distributed Au nanoelectrodes in the insulating matrix, as confirmed by COMSOL simulation. Our findings highlight the potential of nanostructure design for precise control of filamentary-type resistive switching devices.
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We investigated prognostic factors in 42 anaplastic thyroid carcinoma (ATC) patients from a single institution over a 30-year period and explored the use of risk grouping to guide therapeutic decisions. Univariable and multivariable differences in overall survival (OS) were evaluated using the Kaplan-Meier method and the log-rank test as well as Cox proportional hazards model. Risk grouping in making therapeutic decisions for ATC patients was explored. The 1- and 3-year OS rates were 28.6 % and 18.5 %, respectively. Univariate analysis indicated that 4 pre-therapeutic factors of patients were related to poorer prognoses: age ≥ 55 years, white blood cell count ≥ 10.0 × 10(9)/L, blood platelet count ≥ 300.0 × 10(9)/L and advanced clinical tumor-node-metastasis stage. These factors were used to calculate the risk indices. Patients with total risk index scores of no more than 1 were considered to be in the low-risk group, and patients with scores ≥ 2 were considered to be in the high-risk group. The patients in the low-risk group had significantly better 1- and 3-year OS rates (90.9 % and 63.6 %, respectively) than those in the high-risk group (6.5 % and 3.2 %, respectively). Risk group and therapeutic regimen were the 2 factors that independently influenced survival according to multivariable analysis. Surgery that was combined with postoperative radiotherapy significantly benefited the patients in the low-risk group rather than the patients in the high-risk group. Risk grouping was a helpful tool of evaluating the prognoses and guiding the treatment of ATC patients.
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Medição de Risco , Carcinoma Anaplásico da Tireoide/terapia , China/epidemiologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Carcinoma Anaplásico da Tireoide/mortalidadeRESUMO
Hyperbolic metamaterials (HMM) possess significant anisotropic physical properties and tunability and thus find many applications in integrated photonic devices. HMMs consisting of metal and dielectric phases in either multilayer or vertically aligned nanocomposites (VAN) form are demonstrated with different hyperbolic properties. Herein, self-assembled HfO2 -Au/TiN-Au multilayer thin films, combining both the multilayer and VAN designs, are demonstrated. Specifically, Au nanopillars embedded in HfO2 and TiN layers forming the alternative layers of HfO2 -Au VAN and TiN-Au VAN. The HfO2 and TiN layer thickness is carefully controlled by varying laser pulses during pulsed laser deposition (PLD). Interestingly, tunable anisotropic physical properties can be achieved by adjusting the bi-layer thickness and the number of the bi-layers. Type II optical hyperbolic dispersion can be obtained from high layer thickness structure (e.g., 20 nm), while it can be transformed into Type I optical hyperbolic dispersion by reducing the thickness to a proper value (e.g., 4 nm). This new nanoscale hybrid metamaterial structure with the three-phase VAN design shows great potential for tailorable optical components in future integrated devices.
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Porcine parvovirus (PPV) is a pathogen of infectious reproductive disease, which can cause stillbirth, mummification, embryo death, and infertility (SMEDI) syndrome in pigs. The objective of this study was to gain new insights into the evolution and phylogeny of the PPV1 genome. In this study, we isolated two new PPV1 (HLJ202108-Y and SDLC202109) from northern China and sequenced their whole genomes. The new isolates were found to have three amino acid substitutions (K195R, K562R, and S578P) in nonstructural protein 1. The VP2 amino acid site contained nine nonsynonymous substitutions, including six substitutions of the Kresse strain corresponding to the NADL-2 strain and three substitutions of A414S, S436T, and N555K. Genetic evolution analysis was conducted on 107 reference sequences available in the GenBank database, and 4-5 PPV1 taxa were defined. The new isolates were in the same phylogenetic cluster as strain 27a. The changes in the cluster, specifically marker amino acids, and their potential role in enhancing pathogenicity are discussed in this study. Furthermore, the evolutionary tree map results showed that the strains in China were evolving in two directions: one was becoming increasingly similar to early NADL-2 strains, while the other was evolving toward 27a-like strains. We also compared the proliferation ability of the isolated strains in susceptible cells by analyzing the multistep growth curves. The results showed that the virulence titer of the mutant strain was high. In summary, this study introduced the latest changes in PPV and discussed the virus characteristics that were considered to affect virulence.
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Parvovirus Suíno , Animais , Suínos , Parvovirus Suíno/genética , Filogenia , Substituição de Aminoácidos , ChinaRESUMO
Enteric glia have been recently recognized as key components of the colonic tumor microenvironment indicating their potential role in colorectal cancer pathogenesis. Although enteric glia modulate immune responses in other intestinal diseases, their interaction with the colorectal cancer immune cell compartment remains unclear. Through a combination of single-cell and bulk RNA-sequencing, both in murine models and patients, here we find that enteric glia acquire an immunomodulatory phenotype by bi-directional communication with tumor-infiltrating monocytes. The latter direct a reactive enteric glial cell phenotypic and functional switch via glial IL-1R signaling. In turn, tumor glia promote monocyte differentiation towards pro-tumorigenic SPP1+ tumor-associated macrophages by IL-6 release. Enteric glia cell abundancy correlates with worse disease outcomes in preclinical models and colorectal cancer patients. Thereby, our study reveals a neuroimmune interaction between enteric glia and tumor-associated macrophages in the colorectal tumor microenvironment, providing insights into colorectal cancer pathogenesis.
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Neoplasias Colorretais , Neuroglia , Transdução de Sinais , Microambiente Tumoral , Animais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Humanos , Microambiente Tumoral/imunologia , Neuroglia/metabolismo , Camundongos , Macrófagos/metabolismo , Macrófagos/imunologia , Receptores de Interleucina-1/metabolismo , Receptores de Interleucina-1/genética , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Interleucina-6/metabolismo , Monócitos/metabolismo , Monócitos/imunologia , Camundongos Endogâmicos C57BL , Comunicação Celular , Diferenciação Celular , Linhagem Celular Tumoral , FemininoRESUMO
Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T-cell activation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that the loss of TXNIP and GDF15 responsiveness to oxaliplatin is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial oxidative stress drives local immune remodeling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.
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BACKGROUND: Longikaurin A is a natural ent-kaurene diterpenoid isolated from Isodon genus. The ent-kaurene diterpenoids isolated from medicinal plants have been shown to have anti-disease effects. The present study was designed to examine the anti-tumour effects of longikaurin A (LK-A) in nasopharyngeal carcinoma in vitro and in vivo. METHODS: Apoptosis and cell cycle arrest were determined by flow cytometry analysis of the cells treated with Longikaurin A. The proteins of apoptosis signaling pathway were detected by western blotting analysis. Finally, we examined whether LK-A exhibits anti-tumour activity in xenograft models. RESULTS: Longikaurin A inhibited the cell growth by inducing apoptosis and cell cycle arrest. At low concentrations, longikaurin A induced S phase arrest and at higher concentrations, longikaurin A induced caspase-dependent apoptosis by regulating apoptotic molecules. Finally, longikaurin A significantly inhibited the tumour growth of CNE2 xenografts in vivo and showed no obvious effect on the body weights of the mice. CONCLUSION: Our results suggest that Longikaurin A exhibited anti-tumour activity in nasopharyngeal carcinoma in vitro and in vivo.
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Antineoplásicos/uso terapêutico , Diterpenos do Tipo Caurano/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos do Tipo Caurano/química , Diterpenos do Tipo Caurano/farmacologia , Camundongos , Camundongos Nus , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/enzimologia , Neoplasias Nasofaríngeas/patologia , Poli(ADP-Ribose) Polimerases/metabolismo , Fase S/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Heteroepitaxial metal-oxide vertically aligned nanocomposites (VAN) have piqued significant interest due to their remarkable vertical interfacial coupling effects, strong structural and property anisotropy, and potential applications in magnetoelectrics, photocatalysts, and optical metamaterials. VANs present a unique pillar-in-matrix structure with uniform but rather random pillar distributions. Achieving a well-controlled pillar growth remains a major challenge in this field. Here, we use BaTiO3 (BTO)-Au as a model VAN system to demonstrate the effects of Au seedings on achieving such pillar-growth control with enhanced ordering and morphology tuning. The Au seedings are introduced using an anodic aluminum oxide (AAO) template through pulsed laser deposition (PLD). TEM characterization reveals that the Au seedings result in straighter and more evenly distributed Au pillars in the BTO matrix compared to those without seeding, with the diameter of the Au seedings increasing with the number of pulses. Additionally, spectroscopic ellipsometry demonstrates distinct permittivity dispersion for all samples. This demonstration lays a foundation for future controlled and selective growth of VAN systems for on-chip integration.
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Nasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor of the head and neck that often exhibits local recurrence and distant metastasis. The molecular mechanisms are understudied, and effective therapeutic targets are still lacking. In our study, we found that the transcription factor ZIC2 was highly expressed in NPC. Although ZIC family members play important roles in neural development and carcinogenesis, the specific mechanism and clinical significance of ZIC2 in the tumorigenesis and immune regulation of NPC remain elusive. Here, we first reported that high expression of ZIC2 triggered the secretion of MCSF in NPC cells, induced M2 polarization of tumor-associated macrophages (TAMs), and affected the secretion of TAM-related cytokines. Mechanistically, ChIP-seq and RNA-seq analyses identified JUNB as a downstream target of ZIC2. Furthermore, ZIC2 was significantly enriched in the promoter site of JUNB and activated JUNB promoter activity, as shown by ChIP-qPCR and luciferase assays. In addition, JUNB and MCSF participated in ZIC2-induced M2 TAMs polarization. Thus, blocking JUNB and MCSF could reverse ZIC2-mediated M2 TAMs polarization. Moreover, Kaplan-Meier survival analyses indicated that high expression of ZIC2, JUNB, and CD163 was positively associated with a poor prognosis in NPC. Overexpression of ZIC2 induced tumor growth in vivo, with the increase of JUNB, MCSF secretion, and CD163. In summary, our study implies that ZIC2 induces M2 TAM polarization, at least in part through regulation of JUNB/MCSF and that ZIC2, JUNB, and CD163 can be utilized as prognostic markers for NPC and as therapeutic targets for cancer immunotherapy.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Carcinogênese , Neoplasias Nasofaríngeas/genética , Macrófagos , Proteínas Nucleares , Fatores de Transcrição/genéticaRESUMO
Metamaterials present great potential in the applications of solar cells and nanophotonics, such as super lenses and other meta devices, owing to their superior optical properties. In particular, hyperbolic metamaterials (HMMs) with exceptional optical anisotropy offer improved manipulation of light-matter interactions as well as a divergence in the density of states and thus show enhanced performances in related fields. Recently, the emerging field of oxide-metal vertically aligned nanocomposites (VANs) suggests a new approach to realize HMMs with flexible microstructural modulations. In this work, a new oxide-metal metamaterial system, CeO2-Au, has been demonstrated with variable Au phase morphologies from nanoparticle-in-matrix (PIM), nanoantenna-in-matrix, to VAN. The effective morphology tuning through deposition background pressure, and the corresponding highly tunable optical performance of three distinctive morphologies, were systematically explored and analyzed. A hyperbolic dispersion at high wavelength has been confirmed in the nano-antenna CeO2-Au thin film, proving this system as a promising candidate for HMM applications. More interestingly, a new and abnormal in-plane epitaxy of Au nanopillars following the large mismatched CeO2 matrix instead of the well-matched SrTiO3 substrate, was discovered. Additionally, the tilting angle of Au nanopillars, α, has been found to be a quantitative measure of the balance between kinetics and thermodynamics during the depositions of VANs. All these findings provide valuable information in the understanding of the VAN formation mechanisms and related morphology tuning.
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Accumulating evidence indicates that N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play crucial roles in cancer development. However, the biological roles of m6A and lncRNAs in lung cancer tumorigenesis are largely unknown. In this study, SVIL antisense RNA 1 (SVIL-AS1) was downregulated in lung adenocarcinoma (LUAD) tissues and was associated with a favorable prognosis in patients with LUAD. SVIL-AS1 overexpression suppressed LUAD cell proliferation and blocked cell cycle arrest. Mechanistically, METTL3 increased the m6A modification and transcript stability of SVIL-AS1. The enhanced SVIL-AS1 expression mediated by METTL3 suppressed E2F1 and E2F1-target genes. Moreover, SVIL-AS1 accelerated E2F1 degradation. The reduction in cell proliferation induced by SVIL-AS1 overexpression could be rescued by E2F1 overexpression or METTL3 knockdown. In conclusion, our work demonstrated the role and mechanism of METTL3-induced SVIL-AS1 in LUAD, which connects m6A and lncRNA in lung cancer carcinogenesis.
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Adenocarcinoma de Pulmão/patologia , Adenosina/análogos & derivados , Fator de Transcrição E2F1/genética , Neoplasias Pulmonares/patologia , Proteínas de Membrana/genética , Proteínas dos Microfilamentos/genética , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenosina/fisiologia , Proliferação de Células/genética , Fator de Transcrição E2F1/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/metabolismo , Metiltransferases/fisiologia , Proteínas dos Microfilamentos/metabolismo , Estabilidade de RNA/genética , RNA Antissenso/genética , RNA Antissenso/metabolismo , RNA Antissenso/fisiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/fisiologia , Células Tumorais CultivadasRESUMO
Purpose: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC.Experimental Design: RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies. MTT assay, colony formation assay, sphere formation assay, co-immunoprecipitation, chromatin immunoprecipitation assay, and in vivo chemoresistance assay were applied to explore the function of RARS-MAD1L1 in NPC.Results: We demonstrated that RARS-MAD1L1 was present in 10.03% (35/349) primary NPC biopsies and 10.7% (9/84) in head and neck cancer (HNC) samples. RARS-MAD1L1 overexpression increased cell proliferation, colony formation, and tumorigenicity in vitro, and the silencing of endogenous RARS-MAD1L1 reduced cancer cell growth and colony formation in vitro In addition, RARS-MAD1L1 increased the side population (SP) ratio and induced chemo- and radioresistance. Furthermore RARS-MAD1L1 interacted with AIMP2, which resulted in activation of FUBP1/c-Myc pathway. The silencing of FUBP1 or the administration of a c-Myc inhibitor abrogated the cancer stem cell (CSC)-like characteristics induced by RARS-MAD1L1. The expression of c-Myc and ABCG2 was higher in RARS-MAD1L1-positive HNC samples than in negative samples.Conclusions: Our findings indicate that RARS-MAD1L1 might contribute to tumorigenesis, CSC-like properties, and therapeutic resistance, at least in part, through the FUBP1/c-Myc axis, implying that RARS-MAD1L1 might serve as an attractive target for therapeutic intervention for NPC. Clin Cancer Res; 24(3); 659-73. ©2017 AACR.
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Arginina-tRNA Ligase/genética , Proteínas de Ciclo Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Carcinoma Nasofaríngeo/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica , Animais , Arginina-tRNA Ligase/metabolismo , Biomarcadores Tumorais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Camundongos , Carcinoma Nasofaríngeo/diagnóstico , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/genéticaRESUMO
Colorectal cancer (CRC) cells undergo apoptosis in the presence of the small-molecule inhibitor ABT-263 by up-regulating antiapoptotic Bcl-2 family members. However, the resistance to ABT-263 gradually developed in most solid tumors due to its low affinity to Mcl-1. Here, we found the BET-Bromodomain inhibitor JQ1, when combined with ABT-263, synergistically reduced Mcl-1 protein level, induced apoptosis, and decreased cell viability in the CRC HCT-15, HT-29 and SW620 cells. The subsequent mechanism study revealed that a pathway of c-Myc/miR-1271-5p/Noxa/Mcl-1 underlies the synergistic effect of such combination treatment. We discovered that miR-1271-5p, the key mediator for the synergistic effect, is transcriptionally activated by c-Myc, and binds to the 3'-UTR of noxa to inhibit its protein production. The combination treatment of JQ1 and ABT-263 inhibited c-Myc protein level and also c-Myc-driven expression of miR-1271-5p, subsequently increased the protein level of Noxa, and finally promotes the degradation of Mcl-1. Our findings provide an alternative strategy to resolve the resistance during treatment of CRC by JQ1, and also discovered a novel miR-1271-5p-dependent regulatory mechanism for gene expression of noxa.
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Compostos de Anilina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Sulfonamidas/uso terapêutico , Compostos de Anilina/farmacologia , Apoptose/efeitos dos fármacos , Azepinas/farmacologia , Sequência de Bases , Linhagem Celular Tumoral , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sulfonamidas/farmacologia , Triazóis/farmacologiaRESUMO
The autophagy-related gene Beclin-1 is critical in the regulation of tumourigenesis and progression, but its role in oral tongue squamous cell carcinoma (OTSCC) has not yet been reported. This study aimed to investigate Beclin1 expression and its significance in OTSCC. Beclin1 expression was assessed by reverse transcriptionquantitative polymerase chain reaction or western blot analysis in 14 OTSCC tissues and matched adjacent noncancerous tissues as well as in 5 OTSCC cell lines and a normal tongue epithelial cell line. Beclin1 protein expression was examined by immunohistochemistry in 133 OTSCC specimens, and the correlation between Beclin1 expression and clinicopathological features was investigated. Furthermore, MTT and colony formation assays were performed to investigate the effect of Beclin1 on the proliferation and clonogenicity of OTSCC cells. It was demonstrated that Beclin1 expression was significantly decreased in the majority of the 14 OTSCC tissues and the 5 OTSCC cell lines relative to the matched noncancerous tissues and the normal tongue epithelial cell line, respectively. Immunohistochemistry analysis revealed that decreased Beclin1 expression was significantly correlated with poor differentiation, lymph node metastasis, advanced clinical tumournodemetastasis stage, and a poor prognosis in patients with OTSCC. The in vitro assays indicated that the overexpression of Beclin1 significantly inhibits the proliferation and clonogenicity of OTSCC cells. These results demonstrate that Beclin1 acts as a tumour suppressor in the development or progression of OTSCC and that Beclin1 may represent a novel prognostic marker for patients with OTSCC.
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Proteína Beclina-1/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Neoplasias da Língua/genética , Neoplasias da Língua/mortalidade , Autofagia , Proteína Beclina-1/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida , Neoplasias da Língua/patologiaRESUMO
Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, we found that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1α activation. Furthermore, the resultant increase in IL-11 expression significantly induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by Akt/GSK3ß pathway activation and increased invasive and migratory abilities. Conversely, HIF-1α or IL-11 knockdown, or treating cells with a neutralizing antibody against IL-11, a PI3K inhibitor, or Akt inhibitor V, significantly suppressed the induction of EMT and counteracted the enhancements in invasive and migratory abilities. These results indicate that hypoxia increases IL-11 secretion in ATC cells via HIF-1α induction and that IL-11 then induces EMT in these cells via the PI3K/Akt/GSK3ß pathway, ultimately improving their invasive and migratory potential. This study elucidates the prometastatic role played by IL-11 in ATC metastasis and indicates it as a potential target for the treatment of cancer metastasis. However, many questions remain to be explored.
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Transição Epitelial-Mesenquimal , Glicogênio Sintase Quinase 3 beta/metabolismo , Interleucina-11/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Hipóxia Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Células HEK293 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-11/genética , Interleucina-11/farmacologia , Masculino , Pessoa de Meia-Idade , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
BATF2, also called SARI, is associated with several cancer types, and loss of BATF2 expression is frequently detected in aggressive and metastatic cancers. The expression of BATF2 was previously shown to slow the growth rate of malignant tumor cells injected into athymic nude mice, and decreased expression of BATF2 has been correlated to poor prognosis in hepatocellular carcinoma. However, the functional role of BATF2 in oral tongue squamous cell carcinoma (OTSCC) remains unknown. In the present study, we examined BATF2 expression in 16 fresh, paired OTSCC and adjacent non-tumor tissues, as well as in a normal tongue epithelial cell line and in 5 OTSCC cell lines by quantitative PCR and western blot analysis. We also evaluated BATF2 expression in 202 paraffinembedded OTSCC and 30 adjacent non-tumor samples by immunohistochemistry, and its relationship with clinicopathological features and prognosis was investigated. We found that BATF2 expression was significantly reduced in the majority of the 16 OTSCC tumor tissues and the 5 OTSCC cell lines when compared with the non-tumor tissues and the normal tongue epithelial cell line, respectively. Consistent with these results, our immunohistochemistry analysis revealed that decreased BATF2 expression was present in 124 of the 202 cases and was significantly correlated with poor tumor differentiation (P=0.002). Patients with decreased BATF2 expression showed reduced survival when compared to those with high expression (P<0.001). Multivariate analysis revealed that BATF2 expression is an independent predictor of overall survival (P=0.001). These results demonstrate that BATF2 plays a tumor-suppressor role in the development of OTSCC and that BATF2 may serve as a prognostic biomarker and potential therapeutic target for this disease.
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Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/patologia , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Língua/mortalidade , Adulto JovemRESUMO
BACKGROUND: The purpose of this study was to evaluate the outcome in sinonasal mucosal melanoma (SMM). METHODS: A retrospective analysis of clinicopathological data from January 1976 to December 2005 was performed. Survival curve, univariate, and multivariate analyses were undertaken. RESULTS: Sixty-eight patients with SMM were enrolled; 3 patients refused treatment. The 3-year and 5-year overall survival (OS) rates in the remaining 65 cases of SMM were 36.5% and 29.7%, respectively. Patients who underwent surgery had better 3-year and 5-year OS rates than those treated without surgery (40.7% and 34.1% vs 21.4% and 14.3%, respectively), and the same was true for patients treated with and without biotherapy (58.2% and 50.9% vs 30.0% and 23.4%, respectively). Distant metastasis at presentation was associated with a worse prognosis. Those patients managed with multimodality treatment had better OS rates. CONCLUSION: The prognosis in SMM is poor, particularly for those with distant metastasis or without surgery. Multimodality treatment may improve survival.
Assuntos
Melanoma/mortalidade , Melanoma/terapia , Mucosa Nasal/patologia , Neoplasias dos Seios Paranasais/mortalidade , Neoplasias dos Seios Paranasais/terapia , Adolescente , Adulto , Idoso , Análise de Variância , Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Institutos de Câncer , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Intervalos de Confiança , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Interleucina-6/uso terapêutico , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Análise Multivariada , Procedimentos Cirúrgicos Nasais/métodos , Procedimentos Cirúrgicos Nasais/mortalidade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/patologia , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
We have investigated the clinical characteristics and prognostic factors of squamous cell carcinoma (SCC) of the tongue after definitive radiotherapy for nasopharyngeal carcinoma, and evaluated the effect of common therapeutic regimens for these patients. We retrospectively reviewed follow-up data for patients whose nasopharyngeal carcinoma had been treated by radiotherapy, and selected the 68 who had then developed SCC of the tongue, in the border of the tongue in half, and in the dorsum in 25 (37%). Eight of the 68 patients had clinical lymph node metastasis (12%), and 45 presented with stage I-II disease at the time of the diagnosis of the SCC (66%). Resection or radiotherapy alone was an effective treatment for patients with stage I-II SCC of the tongue, but patients with stage III-IV disease had a poor prognosis, despite being given multidisciplinary treatment. Multivariate analysis showed that the risk factors that independently influenced the survival of these patients were use of alcohol, recurrence of their nasopharyngeal carcinoma, the latency period, and the clinical TNM stage. Tongue SCC after radiotherapy was generally at an early stage and commonly occurred on the border or the dorsum of the tongue, with few lymph node metastases. Resection or radiotherapy is an effective treatment, and the risk factors that independently influenced the survival of patients indicate that improving the technique of radiotherapy and close follow-up after nasopharyngeal cancer are vitally important.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Segunda Neoplasia Primária/patologia , Neoplasias da Língua/patologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Carcinoma/patologia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Causas de Morte , Seguimentos , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática/patologia , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fumar , Taxa de Sobrevida , Neoplasias da Língua/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has a poor prognosis, and the consensus on the most effective treatment is needed. METHODS: Clinical data from all ATC patients treated in our institution over a 30-year period (between May 1980 and May 2010) were analyzed retrospectively with regard to mortality and survival rates (Kaplan-Meier). Multivariate analysis was performed using a Cox proportional hazards model. RESULTS: Sixty cases were analyzed. The overall 1- and 3-year survival rates were 35.0% and 22.9%, respectively. Univariate analysis showed that the best prognosis was seen in patients younger than 55 years, those without distant metastases, those with white blood cell (WBC) counts < 10.0 × 10(9)/L or blood platelet (PLT) counts < 300.0 × 10(9)/L at presentation, those who did not receive chemotherapy, and those who received radiotherapy doses ≥ 40 Gy or underwent surgery plus postoperative radiotherapy. According to multivariate analysis, the WBC count at first presentation and the type of therapeutic regimen independently influenced survival. CONCLUSIONS: We found that the elevated peripheral PLT count may be an adverse prognostic factor of ATC patients. The prognosis for ATC is especially poor for patients with distant metastasis, a WBC count ≥ 10.0×10(9)/L, a PLT count ≥ 300.0 × 10(9)/L, or age ≥ 55 years. WBC count at presentation and surgery with or without postoperative radiotherapy independently influenced the prognosis. Intensive treatment combining surgery with postoperative radiotherapy is recommended for ATC patients with stage IVA/B disease.