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Objective: To investigate the correlation between programmed death ligand 1(PD-L1), tumor mutation burden (TMB) and the short-term efficacy and clinical characteristics of anti-PD-1 immune checkpoint inhibitor combination chemotherapy in NSCLC patients. The efficacy of the prediction model was evaluated. Methods: A total of 220 NSCLC patients receiving first-line treatment with anti-PD-1 immune checkpoint inhibitor combined with chemotherapy were retrospectively collected. The primary endpoint was short-term efficacy ORR. The correlation between short-term efficacy, PD-L1, TMB, and clinical characteristics using χ2 test or t-test was evaluated. Screen the independent prognostic factors using univariate and multivariate logistic regression analyses, and construct a nomogram prediction model using the "rms" package in R software. Using receiver operating characteristic (ROC) curve analysis to evaluate the independent Prognostic factors and the prediction model. Using decision curve analysis (DCA) to verify the superiority of the prediction model. Results: The mean values of PD-L1, TMB, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, and albumin were the highest in the ORR group, PD-L1 expression and TMB correlated with epidermal growth factor receptor expression. Multivariate analyses showed that PD-L1, TMB, and neutrophil were independent prognostic factors for ORR. The area under the ROC curve (AUC) values of the ROC constructed based on these three indicators were 0.7104, 0.7139, and 0.7131, respectively. The AUC value under the ROC of the nomogram model was 0.813. The DCA of the model showed that all three indicators used together to build the prediction model of the net return were higher than those of the single indicator prediction model. Conclusion: PD-L1, TMB, and neutrophils are independent prognostic factors for short-term efficacy. The nomogram prediction model constructed using these three indicators can further improve predictive efficacy of ICIs in patients with NSCLC.
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In vivo monitoring of treatment response is of great significance for tumor therapy in clinical trials, but it remains a formidable challenge. Herein, we demonstrate a logic AND gate theranostic nanoagent that responds to the coexistence of endogenous and exogenous stimuli, namely HAuCl4@1-Tetradecanol@Gd-based metal-organic framework@SiO2 nanocomposites (APGS NCs). Upon microwave (MW) irradiation, HAuCl4 in the inner part of APGS NCs reacts with the tumor-associated glutathione (GSH). Subsequently, it transforms into an active luminescent form of Au@1-Tetradecanol@Gd-MOF@SiO2 nanocomposites (AuPGS NCs). The intensity of generated fluorescence is correlated with the tumor thermal-injury status. Thus, the generation of AuPGS NCs with high intensity fluorescence under the co-activation of MW and GSH can visualize the treatment effects during MW thermal therapy and instantly modulate the irradiation time and range for optimal outcomes. Hence, this logic gate controlled APGS NCs makes MW thermal therapy eliminate tumor cells completely. This research offers an effective strategy for the design and preparation of activatable theranostic nanoagents for precise tumor imaging and therapy.
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Neoplasias , Medicina de Precisão , Humanos , Micro-Ondas , Dióxido de Silício , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/patologia , Nanomedicina Teranóstica/métodos , Linhagem Celular TumoralRESUMO
BACKGROUND: Extracellular vesicles (EVs) can be secreted by a wide variety of cells, including tumor cells, and contain some bioactive molecules from the source cells. Therefore, they can potentially be used as biomarkers for early diagnosis of tumors and for tumor therapy. In addition, EVs can affect the features of target cells and participate in regulating the development process of tumors. METHODS: A literature review was conducted to elucidate the role of extracellular vesicles in the progression and treatment of nasopharyngeal carcinoma. RESULTS: In this review, we discuss the molecular mechanisms of cell proliferation, angiogenesis, epithelial-mesenchymal transformation and metastasis, immune response, and chemo-radiotherapy resistance that are induced by EVs. We also reviewed the potential applications of EVs as biomarkers, therapeutic agents, and carriers so as to determine new directions for the early diagnosis and targeted therapy of nasopharyngeal carcinoma. The application limitations have also been discussed in this review, further work is needed to ensure optimal outcomes for patients. CONCLUSION: Although the roles of extracellular vesicles in the progression of nasopharyngeal carcinoma have been summarized, some aspects are still unclear and need to be further studied. In addition, the applications of extracellular vesicles in the treatment of nasopharyngeal carcinoma still need to optimize conditions to produce better therapeutic outcomes for patients with nasopharyngeal carcinoma.
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Vesículas Extracelulares , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Vesículas Extracelulares/metabolismo , Biomarcadores/metabolismo , Transporte Biológico , Neoplasias Nasofaríngeas/patologiaRESUMO
OBJECTIVE: To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS. RESULTS: The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high ß2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL. CONCLUSION: Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.
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Linfoma Extranodal de Células T-NK , Monócitos , Humanos , Monócitos/patologia , Neutrófilos , Linfoma Extranodal de Células T-NK/patologia , Estudos Retrospectivos , Linfócitos , PrognósticoRESUMO
Abnormal long non-coding RNAs (lncRNAs) have been detected in esophageal squamous cell carcinoma (ESCC). Here, we focused on lncRNA ZNF667-AS1 and its downstream mechanism in ESCC progression. Differentially expressed lncRNAs in ESCC were predicted by bioinformatics analysis. ZNF667-AS1, microRNA-1290 (miR-1290), and prune homolog 2 with BCH domain (PRUNE2) expression was determined with their relationship in cell biological processes analyzed also by means of gain- and loss-of-function assays. Xenograft mouse models were performed to re-produce the in vitro findings. We found a decline in ZNF667-AS1 expression in ESCC tissues and cell lines. ZNF667-AS1 overexpression indicated a favorable prognosis of ESCC sufferers. ZNF667-AS1 overexpression suppressed ESCC cell malignant potentials. ZNF667-AS1 reduced miR-1290 to result in upregulation of the miR-1290 target gene PRUNE2. The inhibiting property of ZNF667-AS1 on the malignant characteristics of ESCC cells was achieved by disrupting the miR-1290-mediated downregulation of PRUNE2. ZNF667-AS1 suppressed the tumorigenesis of ESCC in vivo. Collectively, our study demonstrates that ZNF667-AS1 can function as a tumor suppressor in ESCC by upregulating PRUNE2 and downregulating miR-1290.
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Compelling evidence has indicated the vital role of lysine-specific demethylase 4 A (KDM4A), hypoxia-inducible factor-1α (HIF1α) and the mechanistic target of rapamycin (mTOR) signaling pathway in nasopharyngeal carcinoma (NPC). Therefore, we aimed to investigate whether KDM4A affects NPC progression by regulating the HIF1α/DDIT4/mTOR signaling pathway. First, NPC and adjacent tissue samples were collected, and KDM4A protein expression was examined by immunohistochemistry. Then, the interactions among KDM4A, HIF1α and DDIT4 were assessed. Gain- and loss-of-function approaches were used to alter KDM4A, HIF1α and DDIT4 expression in NPC cells. The mechanism of KDM4A in NPC was evaluated both in vivo and in vitro via RT-qPCR, Western blot analysis, MTT assay, Transwell assay, flow cytometry and tumor formation experiments. KDM4A, HIF1α, and DDIT4 were highly expressed in NPC tissues and cells. Mechanistically, KDM4A inhibited the enrichment of histone H3 lysine 9 trimethylation (H3K9me3) in the HIF1α promoter region and thus inhibited the methylation of HIF1α to promote HIF1α expression, thus upregulating DDIT4 and activating the mTOR signaling pathway. Overexpression of KDM4A, HIF1α, or DDIT4 or activation of the mTOR signaling pathway promoted SUNE1 cell proliferation, migration, and invasion but inhibited apoptosis. KDM4A silencing blocked the mTOR signaling pathway by inhibiting the HIF1α/DDIT4 axis to inhibit the growth of SUNE1 cells in vivo. Collectively, KDM4A silencing could inhibit NPC progression by blocking the activation of the HIF1α/DDIT4/mTOR signaling pathway by increasing H3K9me3, highlighting a promising therapeutic target for NPC.
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Carcinogênese/patologia , Movimento Celular , Histona Desmetilases com o Domínio Jumonji/metabolismo , Carcinoma Nasofaríngeo/enzimologia , Carcinoma Nasofaríngeo/patologia , Adulto , Idoso , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Histonas/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Lisina/metabolismo , Masculino , Metilação , Camundongos Nus , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Invasividade Neoplásica , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Cima/genética , Adulto JovemRESUMO
Tumor migration and invasion are key pathological processes that contribute to cell metastasis as well as treatment failure in patients with malignant tumors. However, the mechanisms governing tumor cell migration remain poorly understood. By analyzing the tumor-related database and tumor cell lines, we found that preoptic regulatory factor-2 (Porf-2) is downexpressed in both neuroblastoma and glioma. Using in vitro assays, our data demonstrated that the expression of Porf-2 inhibits tumor cell migration both in neuroblastoma and glioma cell lines. Domain-mutated Porf-2 plasmids were then constructed, and it was found that the GAP domain, which plays a role in the inactivation of Rac1, is the functional domain for inhibiting tumor cell migration. Furthermore, by screening potential downstream effectors, we found that Porf-2 can reduce MMP-2 and MMP-9 expression. Overexpression of MMP-2 blocked the inhibitory effect of Porf-2 in tumor cell migration both in vitro and in vivo. Taken together, we show for the first time that Porf-2 is capable of suppressing tumor cell migration via its GAP domain and the downregulation of MMP-2/9, suggesting that targeting Porf-2 could be a promising therapeutic strategy for nervous system tumors.
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MicroRNA-155 is over-expressed in many human cancers, but researches on its association with malignant oesophageal squamous cell carcinoma (ESCC) are limited. The aim of the present study was to evaluate the potential value of miR-155 as a biomarker for ESCC diagnosis and prognosis. In this study, we found that miR-155 was significantly increased in ESCC tissues compared with the paired adjacent tissues and healthy normal controls (p < .001), according to qRT-PCR, which suggested that miR-155 might act as an oncogene in ESCC. In addition, clinical features such as the depth of tumour invasion, tumour size, and TNM stage were all proved to impact the expression of miR-155 (p < .01). Then, ROC curve analysis, reaching an AUC of 0.870, and a sensitivity and specificity of 83.5% and 77.5%, respectively, revealed that miR-155 was a predictive factor for ESCC. As well, high expression of miR-155 was associated with poor overall survival of the patients (log-rank test, p = .004), according to Kaplan-Meier analysis. MiR-155 might be an independent predictor for overall survival in ESCC patients, manifested by Cox regression analysis (HR = 16.94, 95%CI = 3.33-86.12, p = .001). Taken together, miR-155 could be an independent diagnostic and prognostic biomarker for ESCC.
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Biomarcadores Tumorais/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/genética , MicroRNAs/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) has been reported to participate in the occurrence and development of glioma. However, the function and underlying molecular mechanisms of SNHG5 in glioma remain largely unknown. The expressions of SNHG5, microRNA-1297 (miR-1297) and karyopherin subunit alpha 2 (KPNA2) in glioma tissues and cells were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) or western blot. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect cell viability and apoptosis, respectively. Western blot was also performed to detect the expressions of autophagy-associated proteins. The relationship among lncRNA SNHG5, miR-1297 and KPNA2 was verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. SNHG5 and KPNA2 were over expressed, and the level of miR-1297 was down-regulated in glioma tissues and cell lines. Knockdown of SHNG5 promoted apoptosis, while suppressing cell viability and autophagy of A172 and LN340 cells. Meanwhile, SHNG5 harbored the binding sites with miR-1297, and a negative correlation between the expression of SNHG5 and miR-1297 in glioma tissues was also observed. Interestingly, silencing of miR-1297 undermined the SHNG5 depletion-mediated effect on cell viability, apoptosis, and autophagy. KPNA2 was a direct target of miR-1297, and negatively regulated by miR-1297. More importantly, gain of KPNA2 mitigated the effect of SHNG5l knockdown on glioma cells. Silencing of SNHG5 had an implication in inhibiting apoptosis and stimulating cell viability and autophagy by the miR-1297/KPNA2 axis in glioma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Linfoma Extranodal de Células T-NK/terapia , Neoplasias Nasais/terapia , Adolescente , Adulto , Idoso , Asparaginase/administração & dosagem , Criança , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Extranodal de Células T-NK/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/patologia , Polietilenoglicóis/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem , GencitabinaRESUMO
Long non-coding RNAs (lncRNAs) have been widely highlighted due to their involvement in various types of cancers, including glioma; however, the exact mechanism and function by which they operate in regard to spinal cord glioma remain poorly understood. LOC101928963 was screened out for its differential expression in spinal cord glioma by microarray analysis. Therefore, this study was conducted to investigate the modulatory effects of LOC101928963 on spinal cord glioma by binding to phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1). The expression of LOC101928963 and LOC101928963 was characterized in spinal cord glioma tissues, and their interaction was examined by dual-luciferase reporter gene assay. Cells with LOC101928963 that exhibited elevated or suppressed levels of PMAIP1 were established to substantiate the mechanism between LOC101928963 and PMAIP1. qRT-PCR and western blot methods were subsequently applied to determine the expression of cell-proliferation- and apoptosis-related genes in response to the alterations of LOC101928963 and PMAIP1. Glioma cell proliferation and apoptosis were assessed by MTT assay and flow cytometry. Decreased cell apoptosis and PMAIP1 expression, as well as overexpressed LOC101928963, were exhibited among spinal cord glioma tissues. LOC101928963 overexpression was observed to promote cell proliferation and cell-cycle entry and inhibit the process of apoptosis. PMAIP1, a target of LOC101928963, displayed a downregulated level following the elevation of LOC101928963. The present results strongly emphasize the neutralization effect of PMAIP1 overexpression on spinal cord glioma progression induced by the overexpression of LOC101928963. The data obtained during the study highlighted the inhibitory role of LOC101928963 silencing in spinal cord glioma through the increase in PMAIP1, which suggests a potential target in the treatment of spinal cord glioma.
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Nasopharyngeal carcinoma (NPC) is a malignant epithelial cancer of the head and neck with high prevalence in southern China, which is accompanied by notable invasiveness and metastasis. Long noncoding RNAs (lncRNAs) participate in the progression of various cancers including NPC. Microarray-based analysis identified highly expressed lncRNA mothers against decapentaplegic homolog 5 (SMAD5)-antisense RNA 1 (AS1) related to NPC. Interestingly, it is found that SMAD5-AS1 competitively bound to microRNA (miR)-106a-5p to regulate SMAD5. Herein, the study aimed to clarify the role of SMAD5-AS1/miR-106a-5p/SMAD5 axis in the process of epithelial mesenchymal transition (EMT) in NPC. SMAD5-AS1 was highly expressed and miR-106a-5p was poorly expressed in NPC tissues and cell lines. The NPC cells were treated with a series of small interfering RNAs, mimics, or inhibitors to explore the effects of SMAD5-AS1, SMAD5, and miR-106a-5p on EMT, cell proliferation, migration, and invasion in NPC. Of note, SMAD5-AS1 silencing or miR-106a-5p overexpression reduced expression of N-cadherin, matrix metallopeptidase 9, Snail, and Vimentin while elevating E-cadherin expression, thus inhibiting EMT, cell proliferation, migration, and invasion in NPC by down-regulation of SMAD5. Moreover, SMAD5 silencing could reduce the ability of EMT induced by SMAD5-AS1 up-regulation. SMAD5-AS1 silencing or miR-106a-5p elevation inhibited tumorigenesis in nude mice. Taken together, SMAD5-AS1 silencing suppressed EMT, cell proliferation, migration, and invasion in NPC by elevating miR-106a-5p to down-regulate SMAD5, which provided a novel therapeutic target for NPC treatment.-Zheng, Y.-J., Zhao, J.-Y., Liang, T.-S., Wang, P., Wang, J., Yang, D.-K., Liu, Z.-S. Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.
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Transição Epitelial-Mesenquimal/fisiologia , MicroRNAs/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Fatores de Transcrição/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Inativação Gênica , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não CodificanteRESUMO
The pleiotropic effects of hyperthermia on cancer cells have been well documented, and microwave hyperthermia (MWHT) has been widely applied for multifarious cancer treatment. However, the mechanisms underlying the anticancer effect of MWHT combined with gemcitabine (GEM) remain poorly understood. The aim of the present study was to investigate the role of autophagy in the thermochemotherapy of human squamous cell lung carcinoma cells. It was observed that MWHT combined with GEM potently suppressed the viability of NCIH2170 and NCIH1703 cells, and induced G0/G1 cell cycle arrest. Notably, MWHT with GEM induced autophagy, as indicated by the formation of autophagic vacuoles, downregulation of p62 and upregulation of light chain 3II. It was further demonstrated that the autophagy was due to the production of reactive oxygen species (ROS), whereas Nacetyl cysteine, an ROS scavenger, attenuated the level of autophagy. However, when the autophagy inhibitor 3methyladenine was used, there was no significant change in the production of ROS. Furthermore, it was observed that MWHT combined with GEM downregulated the protein expression levels of phosphoinositide 3kinase (PI3K), phosphorylated (p)PI3K, protein kinase B (AKT), pAKT, mammalian target of rapamycin (mTOR), pmTOR, phosphorylated S6 (pS6) and p70 S6 kinase, which are associated with autophagy. In addition, the results demonstrated that ROS served as an upstream mediator of PI3K/AKT/mTOR signaling. In light of these findings, the present study provides original insights into the molecular mechanisms underlying the cell death induced by MWHT combined with GEM, and this may be a promising approach for the treatment of human squamous cell lung carcinoma.
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Autofagia/efeitos da radiação , Carcinoma Pulmonar de Células não Pequenas/terapia , Desoxicitidina/análogos & derivados , Hipertermia Induzida/métodos , Neoplasias Pulmonares/terapia , Adenina/análogos & derivados , Adenina/farmacologia , Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Terapia Combinada/métodos , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Humanos , Neoplasias Pulmonares/patologia , Micro-Ondas/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Serina-Treonina Quinases TOR/metabolismo , GencitabinaRESUMO
Hyaluronan synthase 2 (HAS2)-AS1 (natural antisense transcript of HAS2) functions as oncogenic long noncoding RNA (lncRNA) in oral squamous cell carcinoma, breast cancer, and osteosarcoma. The role of HAS2-AS1 in glioma remains unknown. In our research, HAS2-AS1 expression was elevated in glioma tissues compared with normal brain tissues. Moreover, high levels of HAS2-AS1 expression was observed in patients with glioma with high WHO grade (III-IV) or large tumor size ( > 4 cm). The survival analysis from The Cancer Genome Atlas showed glioma cases with high HAS2-AS1 expression that had shorter disease-free survival time and overall survival time than those with low HAS2-AS1 expression. In vitro studies suggested that knocking down HAS2-AS1 expression inhibited glioma cell viability, migration, and invasion through phosphoinositide 3-kinase/protein kinase B signaling pathway. In conclusion, HAS2-AS1 may be considered as a predictor for clinical outcome and a potential therapeutic target in glioma.
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BACKGROUND: Epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs (miRNAs). This study aims to assess the role of miR-506 working in tandem with LIM Homeobox 2 (LHX2) in EMT and metastasis through the Wnt/ß-catenin signaling pathway in nasopharyngeal carcinoma (NPC). METHODS: Differentially expressed genes associated with NPC were screened using microarray analyses, from which LHX2 was identified. Next, the potential relationship between miR-506 and LHX2 was analyzed. In order to explore the effect of miR-506 or LHX2 on NPC cell proliferation, migration, invasion and apoptosis, serials of mimics, inhibitors or siRNA against LHX2 were transfected into NPC cells. Then, the expression patterns of LHX2, Wnt1, ß-catenin, E-cadherin, Vimentin, TCF4 and Twist were determined to assess the influence of miR-506 or LHX2 on EMT as well as the relationship between the Wnt/ß-catenin signaling pathway and TCF4. The tumorigenicity and lymph node metastasis (LNM) in xenograft tumors of nude mice were observed. RESULTS: The has-miR-506-3p was identified as the down-regulated gene in NPC based on the microarray data while LHX2 was negatively regulated by miR-506. Over-expression of miR-506 or silencing of LHK2 inhibited NPC cell proliferation, migration, invasion, tumorigenicity and LNM but promoted apoptosis indicated by decreased Wnt1, ß-catenin, Vimentin, TCF4 and Twist expressions along with increased E-cadherin expressions. CONCLUSIONS: miR-506 inhibits tumor growth and metastasis in NPC via inhibition of Wnt/ß-catenin signaling by down-regulating LHX2, accompanied by decreased TCF4. Taken together, miR-506 targeted-inhibition LHX2 presents a promising therapeutic strategy for the treatment of NPC. TRIAL REGISTRATION: ChiCTR1800018889 . Registered 15 October 2018.
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Proliferação de Células/genética , Proteínas com Homeodomínio LIM/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Metástase Neoplásica/genética , Fatores de Transcrição/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Adulto , Idoso , Animais , Apoptose/genética , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , RNA Interferente Pequeno/genética , Fator de Transcrição 4/genética , Vimentina/genéticaRESUMO
Lysine demethylase 3A (KDM3A) is been suggested to accelerate tumor cell migration and invasion in breast cancer, cervical cancer, Ewing sarcoma and neuroblastoma. The role of KDM3A in colorectal cancer progression and metastasis remains unknown. The aim of this study is to explore the clinical significance and biological function of KDM3A in colorectal cancer. In our results, we found KDM3A expression was significantly increased in colorectal cancer metastatic lesions compared with primary lesions, but had no statistical difference between colorectal cancer tissues and normal colorectal tissues. Moreover, high KDM3A expression was correlated with poor histological differentiation, and advanced clinical stage, N classification, M classification and short overall survival in colorectal cancer patients. Univariate and multivariate Cox proportional hazards regression analyses indicated that high expression of KDM3A served as an independent unfavorable prognostic factor in colorectal cancer patients. The loss-of-function and gain-of-function studies showed KDM3A functioned as oncogene to regulate colorectal cancer cell migration and invasion through modulating EMT and MMPs. In conclusion, KDM3A is a promising therapeutic target for preventing metastasis and improving prognosis in colorectal cancer.
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Movimento Celular , Neoplasias Colorretais/patologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , PrognósticoRESUMO
BACKGROUND: Intensity-modulated radiation therapy (IMRT) has been more widely used in extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) because it can maximally improve the local control rate of tumor and reduce the radiation dose received by surrounding normal tissues. However, there has been no consensus on whether IMRT can help to lower the toxic and adverse reactions caused by radiation therapy. The aim of this study is to compare skin toxicity caused by IMRT and conventional radiotherapy in Stage I-II NKTCL. METHODS: A total of 93 patients with Stage I-II NKTCL, nasal-type arising in the nasal cavity were consecutively treated using curative radiotherapy between April 2005 and August 2014. These patients received radiotherapy without chemotherapy. Definitive radiotherapy was conducted using conventional radiotherapy in 33 patients and IMRT in the other sixty patients with a regional field and a total dose of 50 Gy. Dosimetric parameters of radiation treatment plans and skin toxicity were analyzed and compared between conventional radiotherapy and IMRT. RESULTS: From the dosimetric analysis, IMRT demonstrated significantly improved dose coverage and homogeneity than conventional radiotherapy. Meanwhile, the Grade 1, 2, and 3 skin toxicity incidences in conventional radiotherapy group were 42.4%, 39.4%, and 18.2%, and in IMRT group were 25.0%, 31.7%, and 43.3%, respectively. Our data suggested that the severity of skin toxicity in IMRT group was statistically higher than that in conventional radiotherapy group. CONCLUSIONS: IMRT provided improved dose coverage than conventional radiotherapy. However, IMRT failed to lower patients' risks for skin toxicity and may have the potential to increase skin toxicity.
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Linfoma Extranodal de Células T-NK/radioterapia , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/epidemiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Pele/efeitos da radiação , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/patologia , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Cytokines are known as important regulators of the cancer involved in inflammatory and immunological responses. This fact and plethora of gene polymorphism data prompted us to investigate IL1 gene polymorphisms in breast cancer (BC) patients. Totally, 530 patients with BC and 628 healthy control women were studied. The genetic polymorphisms for IL1 were analyzed by Massarray Sequencing method. Three single nucleotide polymorphisms (SNPs) identified in IL1B, IL1R1 gene are thought to influence breast cancer risk. The results of the association between IL-1B, IL1R1 polymorphisms and breast cancer risk have significant. We found that the variant TT genotype of rs10490571 was associated with a significantly increased breast cancer risk (TT vs. CC: OR = 2.82, 95% CI = 1.12-7.08, P = 0.047 for the codominant model). For rs16944 (AG vs. GG: OR = 0.60, 95% CI = 0.41-0.90, P = 0.034 for the codominant model) and rs1143623 (CG vs. CC: OR = 0.65, 95% CI = 0.45-0.94, P = 0.023 for the codominant model) have significant associations were found in genetic models. In conclusion, the present analysis suggests a correlation of polymorphic markers within the IL-1 gene locus with the risk in developing breast cancer. Taken together with our finding that IL1B, IL1R1 gene three SNP are also associated with the risk for the disease, we suggest that inflammation via innate and adaptive immunity contributes to multifactorial hereditary predisposition to pathogenesis of the breast cancer.
RESUMO
BACKGROUND: The interleukins (ILs) are a large family of endogenous cytokines that are crucial in the regulation of inflammation and immunological responses. The IL-1 receptor antagonist (IL-1RN) has been found to be associated with risk breast cancer (BC) in Korean and Indian women. However, little information is found about the polymorphisms of IL-1RN in Chinese Han BC patients. METHODS: We investigated the association between single-nucleotide polymorphisms (SNPs) in IL-1RN and BC risk in a case-control study that included 530 BC cases and 628 healthy controls. Six tag SNPs in IL-1RN were selected and genotyped using the Sequenom MassARRAY platform (Sequenom, San Diego, CA, USA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and sex. RESULTS: In the allele model, we found that the frequency of the 'T' allele of rs928940 was significantly lower in BC cases than in controls (OR = 0.776, 95% CI = 0.611-0.985, p = 0.037). In the genetic model analysis, five susceptibility SNPs were found to be associated with BC risk: the minor allele 'G' of rs315919, rs3181052 and rs452204 were associated with a decreased risk of BC under dominant model (p < 0.05), whereas the minor alleles 'T' and 'C' of rs928940 and rs4252019 were associated with a decreased risk of BC under both the codominant and dominant models (p < 0.05), which suggested these SNPs may play a protective role against BC risk. The haplotype 'TAGC' constructed by rs928940, rs3181052, rs452204 and rs4252019 was associated with a decreased risk of BC (OR = 0.33; 95% CI = 0.12-0.94; p = 0.038). CONCLUSIONS: The data obtained in the present study shed new light on the association between genetic polymorphisms of IL-1RN and BC susceptibility in the Chinese Han population.