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The pathogenesis of dyschromatosis symmetrica hereditaria (DSH) has not been well defined. In this study, we sought to investigate the influence of the ADAR1 gene on DSH both in vitro and in vivo. Morpholino knockdown of adar1 in zebrafish produced phenotypes characterized by polarity changes, and abnormal migration and distribution of melanocytes. Differential expression of C-KIT and distinct patterns of apoptosis between hyperpigmented and hypopigmented areas in DSH patient were detected by means of immunohistochemical methods and TUNEL assays, respectively. This study revealed that adar1 knockdown in a zebrafish model resulted in abnormal migration and changes in the cell polarity of melanocytes, and provided novel insight into the mechanism of DSH pathogenesis.
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Adenosina Desaminase , Transtornos da Pigmentação , Proteínas de Ligação a RNA , Peixe-Zebra , Animais , Humanos , Adenosina Desaminase/genética , Mutação , Linhagem , Transtornos da Pigmentação/congênito , Proteínas de Ligação a RNA/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
BACKGROUND: Previous studies indicated CRNDE to have a pivotal part within tumorigenesis. Notwithstanding, precise details on CRNDE activities within NPC are still uncertain. The investigation described in this article served to focus in greater depth on the mechanistics regarding CRNDE, together with all associated regulatory networks, on nasopharyngeal carcinoma (NPC) and its treatment possibilities. METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) analyzed CRNDE, miR-545-5p and CCND2 expression within NPCs and representative cell lineages. CCK-8 cell counting-, EdU-, wound-healing-/transwell-assays analyzed cellular proliferation, migrative, together with invasive properties. Apoptosis/cell cycle progression were scrutinized through flow cytometry. Dual-luciferase reporter assays validated CRNDE/miR-545-5p/CCND2 interplay. Proteomic expression of apoptosis-related protein, EMT-related protein and CCND2 protein were evaluated through Western blotting. In addition, Ki67 expression was evaluated through immunohistochemical staining. The effect of CRNDE in vivo was assessed by nude murine xenograft model studies. RESULTS: This study demonstrated up-regulated expression of CRNDE and CCND2 within NPC tissues/cell lines. Meanwhile, miR-545-5p was down-regulated. CRNDE knock-down or miR-545-5p over-expression drastically reduced NPC proliferative, migrative and invasive properties, promoted apoptosis/altered cell cycle, and inhibited CCND2 expression. However, miR-545-5p down-regulation had opposing effects. All inhibiting functions generated by CRNDE down-regulation upon NPC progression could be counterbalanced or synergistically exacerbated, depending on miR-545-5p down-regulation or up-regulation, respectively. Multiple-level investigations revealed CRNDE to serve as a sponge for miR-545-5p, and can target CCND2 within NPCs. CONCLUSIONS: CRNDE increases CCND2 expression by competitive binding with miR-545-5p, thus accelerating the development of NPC. This provides potential therapeutic targets and prognostic markers against NPC.
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Regulatory T cells (Tregs) play an essential role during homeostasis and tolerance of the immune system. Based on our previous study that exposure of pregnant rats to staphylococcal enterotoxin B (SEB) can alter the percentage of CD4/CD8 subsets in the thymus of the offspring, in this study, we focus on the influence of exposure of pregnant rats to SEB on number, function and response of Tregs in the thymus of the offspring. Pregnant rats at gestational day of 16 were intravenously injected with 15 µg SEB and the thymuses of the neonatal and adult offspring were harvested for this study. We found that exposure of pregnant rats to SEB could significantly increase the absolute number of Tregs and the FoxP3 expression level in the thymus of not only neonatal but also adult offspring. Re-exposure of adult offspring to SEB remarkably reduced the suppressive capacity of Tregs to CD4+ T cells and the expression levels of TGF-ß and IL-10 in the thymus, but had no effect on production of IL-4 and IFN-γ. Furthermore, it also notedly decreased the absolute number of Tregs and the FoxP3 expression level. These data suggest that prenatal exposure of pregnant rats to SEB attenuates the response of increased Tregs to re-exposure to SEB in the thymus of adult offspring.
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Enterotoxinas , Linfócitos T Reguladores , Animais , Feminino , Tolerância Imunológica , Gravidez , RatosRESUMO
BACKGROUND: As a natural extraction, astaxanthin is gaining increasing attention because of its safety and anti-tumor properties. It has been reported to participate in the progression of various types of cancer such as gastric cancer and ovarian cancer. Nevertheless, the role of astaxanthin in nasopharyngeal carcinoma (NPC) has not been investigated. OBJECT: The study aimed to explore the anticancer mechanism of astaxanthin in regulating NPC cell proliferation, cell cycle progression, apoptosis, migration, and invasion. METHODS: Human NPC cells (C666-1) were treated with different concentrations of astaxanthin (0, 1, 10, 20 mg/mL) followed by detection of cell viability. Then, C666-1 cell proliferation, apoptosis, cell cycle progression, invasion, and migration in response to 10 mg/mL astaxanthin, LY294002 (PI3K/AKT inhibitor) or parthenolide (PTL; NF-κB inhibitor) treatment were measured using cell counting kit-8 assay, colony forming assay, flow cytometry analyses, Transwell assay, and wound healing assay, respectively. Western blotting was performed to quantify protein levels of factors involved in PI3K/AKT and NF-κB signaling pathways, cell cycle phase markers (Cyclin D1, p21) and apoptotic markers (Bcl-2 and Bax). RESULTS: C666-1 cell proliferation, invasion, and migration were significantly suppressed by astaxanthin while cell apoptosis and cell cycle arrest at G1 phase were effectively enhanced in the context of 10 mg/mL astaxanthin. Protein levels of p-AKT, p-P65 and p-IκB levels were suppressed by astaxanthin treatment. After LY294002 or PTL treatment, the suppressive impact of astaxanthin on C666-1 cell process was strengthened, accompanied by the more obvious decrease in cell activity and cell colony number, more enhanced cell apoptosis and G1 phase arrest, and further inhibited cell migration and invasion. Moreover, the inhibitory effect of astaxanthin on Cyclin D1 and Bcl-2 protein levels as well as the promoting impact of astaxanthin on p21 and Bax were also amplified in combination with LY294002 or PTL treatment. CONCLUSIONS: Astaxanthin significantly suppresses NPC cell proliferation, cell cycle arrest, migration, invasion while promoting cell apoptosis by inactivating PI3K/AKT and NF-κB pathways. The study first reveals the anticancer role of astaxanthin in NPC, providing a potential candidate for NPC treatment.
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Pilon fractures represent a challenging subset of tibial fractures. The management of AO/OTA Type C3 fractures remains complex due to associated complications and lack of clear guidelines for surgical timing and methods. A prospective cohort study was conducted to evaluate two staged treatment strategies for AO/OTA Type C3 tibial pilon fractures. The study focused on assessing surgical difficulty, complications, and patient prognosis. One group of patients received early internal fixation of the fibula and tibial posterior column combined with external fixation, while the other group received external fixation alone in the first stage. Patients who received early internal fixation of the fibula and tibial posterior column combined with external fixation had better outcomes, including lower rate of allogeneic bone grafting (67.74 % versus 94.64 %), reduced incidence of wound delay and skin necrosis (3.23 % versus 21.43 %), shorter surgical time (133.06 ± 23.99 min versus 163.04 ± 26.83 min), shorter hospital stay (13.77 ± 2.53 days versus 18.25 ± 3.67 days), and higher AOFAS (83.05 ± 8.68 versus 79.36 ± 8.92). Additionally, avoiding fibular shortening was shown to be crucial in preventing prolonged surgery and improving patient function. The study demonstrated that the staged treatment approach with early internal fixation led to shorter operative times, improved ankle function, and reduced complications, including a lower risk of infection. The findings support the use of this treatment to optimize outcomes in AO/OTA Type C3 pilon fractures.
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Fraturas do Tornozelo , Traumatismos do Tornozelo , Fraturas da Tíbia , Humanos , Estudos Prospectivos , Resultado do Tratamento , Traumatismos do Tornozelo/cirurgia , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Estudos Retrospectivos , Fixação de FraturaRESUMO
Renal fibrosis is the result of all chronic kidney diseases and is becoming a major global health hazard. Currently, traditional treatments for renal fibrosis are difficult to meet clinical needs due to shortcomings such as poor efficacy or highly toxic side effects. Therefore, therapeutic strategies that target the kidneys are needed to overcome these shortcomings. Drug delivery can be attained by improving drug stability and addressing controlled release and targeted delivery of drugs in the delivery category. By combining drug delivery technology with nanosystems, controlled drug release and biodistribution can be achieved, enhancing therapeutic efficacy and reducing toxic cross-wise effects. This review discusses nanomaterial drug delivery strategies reported in recent years. Firstly, the present review describes the mechanisms of renal fibrosis and anti-renal fibrosis drug delivery. Secondly, different nanomaterial drug delivery strategies for the treatment of renal injury and fibrosis are highlighted. Finally, the limitations of these strategies are also discussed. Investigating various anti-renal fibrosis drug delivery strategies reveals the characteristics and therapeutic effects of various novel nanosystem-derived drug delivery approaches. This will serve as a reference for future research on drug delivery strategies for renal fibrosis treatment.
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Sistemas de Liberação de Medicamentos , Fibrose , Humanos , Fibrose/tratamento farmacológico , Animais , Nefropatias/tratamento farmacológico , Nanoestruturas/química , Portadores de Fármacos/química , Rim/patologia , Rim/efeitos dos fármacosRESUMO
Objective Machine learning was used to screen the key characteristic genes of nasopharyngeal carcinoma (NPC) and analyze their correlation with immune cells. Methods Download the NPC training datasets (GSE12452 and GSE13597) and the validation dataset (GSE53819) from the Gene Expression Omnibus (GEO). Firstly, the training data sets were merged and screened for differentially expressed genes (DEGs); Secondly, the DEGs were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Next, the least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) algorithms were used to identify NPC-related genes in the training datasets and examined in the validation dataset, to further identify key genes using the area under curve (AUC) of receiver operating characteristic curve (ROC); Finally, the correlation between the key genes and immune cells was analyzed. Results A total of 55 DEGs were obtained, including 43 down-regulated genes and 12 up-regulated genes. The GO functions were enriched in humoral immune response, cell differentiation, neutrophil activation and chemokine receptor binding. The KEGG were mainly enriched in the IL-17 signaling pathway. The GSEA was enriched in cell cycle, extracellular matrix receptor interactions, cancer pathways and DNA replication. Immune infiltration analysis showed that the expression of naive B cells, memory B cells, and resting memory CD4+ T cells was significantly lower in NPC, while CD8+ T cells, naive CD4+ T cells, activated memory CD4+ T cells, follicular helper T cells, M0 macrophages and M1 macrophages were highly expressed in NPC. Among the feature genes screened by LASSO and SVM, only CCDC19, LAMB1, SPAG6 and RAD51AP1 genes' AUC were greater than 0.9 in both the training and validation datasets and were closely associated with immune cell infiltration. Conclusion The key genes CCDC19, LAMB1, SPAG6 and RAD51AP1 in NPC development are screened by machine learning algorithms, and are closely associated with immune cell infiltration.
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Linfócitos T CD8-Positivos , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Transdução de Sinais , Aprendizado de Máquina , Neoplasias Nasofaríngeas/genéticaRESUMO
BACKGROUND: CD70 is a costimulatory molecule that is transiently expressed on a small set of activated lymphocytes and is involved in T-cell-mediated immunity. However, the role of CD70 in B-cell malignancies remains controversial. METHODS: We investigated the clinical relevance of CD70 genetic alterations and its protein expression in two diffuse large B-cell lymphoma (DLBCL) cohorts with different ethnic backgrounds. We also performed transcriptomic analysis to explore the role of CD70 alterations in tumour microenvironment. We further tested the blockade of CD70 in combination with PD-L1 inhibitor in a murine lymphoma model. RESULTS: We showed that CD70 genetic aberrations occurred more frequently in the Chinese DLBCL cohort (56/233, 24.0%) than in the Swedish cohort (9/84, 10.8%), especially in those with concomitant hepatitis B virus (HBV) infection. The CD70 genetic changes in DLBCL resulted in a reduction/loss of protein expression and/or CD27 binding, which might impair T cell priming and were independently associated with poor overall survival. Paradoxically, we observed that over-expression of CD70 protein was also associated with a poor treatment response, as well as an advanced disease stage and EBV infection. More exhausted CD8+ T cells were furthermore identified in CD70 high-expression DLBCLs. Finally, in a murine lymphoma model, we demonstrated that blocking the CD70/CD27 and/or PD1/PD-L1 interactions could reduce CD70+ lymphoma growth in vivo, by directly impairing the tumour cell proliferation and rescuing the exhausted T cells. CONCLUSIONS: Our findings suggest that CD70 can play a role in either tumour suppression or oncogenesis in DLBCL, likely via distinct immune evasion mechanisms, that is, impairing T cell priming or inducing T cell exhaustion. Characterisation of specific dysfunction of CD70 in DLBCL may thus provide opportunities for the development of novel targeted immuno-therapeutic strategies.
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Ligante CD27 , Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Animais , Humanos , Camundongos , Linfócitos B/patologia , Ligante CD27/genética , Linfócitos T CD8-Positivos/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Microambiente TumoralRESUMO
BACKGROUND: MicroRNA-34a (miR-34a) has been reported to inhibit TGF-ß (transforming growth factor-ß)-induced epithelial-mesenchymal transition (EMT) in nasopharyngeal carcinoma (NPC). However, the underlying mechanism remain unclear. Using the bioinformatics, we found that the AXL receptor tyrosine kinase (AXL) is a predicted target of miR-34a. OBJECTIVE: we aimed to reveal the relationship between miR-34a and AXL, and investigate the effect and mechanism of miR-34a in NPC progression. METHODS: The expression patterns of miR-34a and AXL in 30 paired NPC tissues and the adjacent tissues were examined by quantitative real time PCR (qRT-PCR). The target relationship between miR-34a and AXL was evaluated by the luciferase gene reporter assay. Cell migration and invasion were assessed by wound healing and transwell chamber assays, respectively. RESULTS: miR-34a level was dramatically decreased in the NPC tissues compared to the adjacent tissues, while AXL expression was increased. Overexpression of miR-34a significantly reduced the luciferase activity of the luciferase vector of AXL (pGL3-AXL-WT), whereas this effect was abrogated when binding sites between miR-34a and AXL were mutated. In addition, ectopic expression of miR-34a dramatically inhibited Sune-1 cell migration and invasion abilities, decreased the levels of N-cadherin and Vimentin and increased E-cadherin and γ-catenin expressions, as well as induced significant reductions in the expressions of p-AKT and Snail. However, these effects were attenuated when the cells were treated with recombinant human AXL protein. CONCLUSIONS: Our results demonstrate that miR-34a/AXL can inhibit NPC cell migration, invasion and EMT through inhibition of AKT/Snail signaling.
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Transição Epitelial-Mesenquimal/genética , MicroRNAs/fisiologia , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptores Proteína Tirosina Quinases/genética , Transdução de Sinais/genética , Transfecção/métodos , Receptor Tirosina Quinase AxlRESUMO
BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer (NSCLC), is poorly differentiated and highly aggressive. Treatment is limited, and the prognosis is poor. Pembrolizumab is an anti-programmed death (PD)-1 antibody with good efficacy in NSCLC. Recent studies have demonstrated that PD-ligand 1 (PD-L1) overexpression is common in PSCs, which suggests that anti-PD-L1 treatment is an ideal option. However, the response to pembrolizumab in PSC has not been studied. CASE SUMMARY: We present a PSC case with PD-L1 overexpression that significantly benefited from pembrolizumab. A 73-year-old Chinese male was detected with a right lung lesion. Pathological analysis of the right upper lobectomy confirmed PSC. The PD-L1 test revealed overexpression (TPS: 90%). Multiple metastases occurred 1 mo after surgery, representing stage IV PSC. Neither first-line chemotherapy nor second-line antiangiogenic agents showed any benefit. Radiotherapy (1200 cGy) was administered to relieve chest wall pain. The patient received the PD-1 inhibitor pembrolizumab (100 mg) as third-line therapy; however, because of fever and severe infection, he refused to receive immunotherapy any longer. Thus, only one dose of pembrolizumab was administered. Deep sustained remission of most of the metastases was achieved except for lesions in the right adrenal gland, which first shrank and then progressed. The patient died because of disease progression in the right adrenal gland. He achieved a progression-free survival time of 8 mo and an overall survival time of 9 mo with third-line pembrolizumab. CONCLUSION: Our findings highlight and offer direct evidence of the efficacy of pembrolizumab in PD-L1-overexpressing PSCs. Combined radiotherapy and immunotherapy may enhance treatment efficacy.
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Objective To explore the effect of miR-129-1-3p on cisplatin sensitivity of chemo-resistant epithelial nasopharyngeal carcinoma HNE19/CDDP cells and the related mechanism. Methods Human nasopharyngeal carcinoma HNE1 cells and cisplatin-resistant HNE19/CDDP cells were cultured. Cisplatin resistance index of cisplatin-resistant HNE1/CDDP cells was tested by MTT assay. The levels of miR-129-1-3p and WEE1 mRNA in HNE1 and HNE19/CDDP cells were measured by real-time quantitative PCR. miR-129-1-3p mimics and unrelated sequence control (miR-129-1-3p NC) were transfected into HNE1/CDDP cells using LipofectamineTM 2000. The drug sensitivity (IC50) of these cells to cisplatin was determined by MTT assay. The protein expression level of WEE1 was determined by Western blot analysis. The 3'-UTR of WEE1 was cloned into luciferase reporter vector and its luciferase activity was detected to verify whether miR-129-1-3p targets WEE1. Results Resistance index of HNE1/CDDP cells to cisplatin was 5.29. The expression level of miR-129-1-3p in the HNE1 cells was significantly higher than that in the HNE1/CDDP cells. The mRNA expression level of WEE1 in the HNE1 cells was lower than that in the HNE1/CDDP cells. The level of miR-129-1-3p was negatively correlated with the level of WEE1 mRNA (r=-0.9784). The IC50 of cisplatin was significantly reduced in the HNE1/CDDP cells after transfected with miR-129-1-3p mimics. The protein expression level of WEE1 in the cells transfected with miR-129-1-3p mimics significantly decreased as compared with the control group and blank group. The miR-129-1-3p regulated the 3'-UTR of WEE1 and reduced the expression activity of luciferase. Conclusion miR-129-1-3p could reverse cisplatin resistance of HNE1/CDDP nasopharyngeal carcinoma cells via inhibiting WEE1 expression.
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Proteínas de Ciclo Celular/antagonistas & inibidores , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Proteínas Tirosina Quinases/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológicoRESUMO
OBJECTIVE: To investigate the correlations of miR-31 expression with cell proliferation, invasion, and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The expression of miR-31 in human laryngeal cancer TU686 cells, human nasopharyngeal carcinoma CNE-2 cells, and normal human oral keratinocyte (NHOK) epithelial cells was detected via quantitative real-time polymerase chain reaction (qRT-PCR). The effects of miR-31 on the proliferation and invasion of HNSCC cells were explored through transfecting miR-31 analogs (miR-31 mimics) and miR-31 inhibitors (anti-miR-31). qRT-PCR was applied to detect the expressions of miR-31 in 56 cases of HNSCC tumor tissues and tumor-adjacent normal tissues. The correlation of miR-31 expression with pathological parameters and survival prognosis of HNSCC patients was also analyzed. RESULTS: The expressions of miR-31 in TU686 and CNE-2 cell lines were significantly higher than that in NHOK cells (p < 0.01). Compared with those in the negative control group, the proliferation and invasion abilities of cells transfected with miR-31 mimics were notably enhanced (p < 0.01), and those of cells transfected with anti-miR-31 were significantly reduced (p < 0.01). In addition, miR-31 mimics significantly reduced ARID1A expression (p < 0.01) and anti-miR-31 increased its expression (p < 0.05). The expression of miR-31 in tumor tissues of HNSCC patients was remarkably higher than that in tumor-adjacent normal tissues (p < 0.01). This, together with clinical data analysis, revealed that the expression of miR-31 was associated with tumor differentiation, metastasis, and staging of patients, and the survival period of patients with lowly expressed miR-31 was longer. CONCLUSIONS: The highly expressed miR-31 can stimulate the proliferation and invasion of HNSCC cells, closely correlated with tumor differentiation, metastasis, and staging of patients. Patients with lowly expressed miR-31 have a longer survival period. Therefore, miR-31 expression can be taken as a crucial reference indicator for the prognosis of HNSCC patients.
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Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores Tumorais/agonistas , Biomarcadores Tumorais/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de SobrevidaRESUMO
MicroRNAs are important factors in the pathogenic processes of human types of cancers including nasopharyngeal carcinoma (NPC). In the present study, we confirmed that the microRNA-212 expression level was significantly decreased both in NPC tissues and NPC cell lines. Decreased expression of miR-212 was associated with advanced tumor-node-metastasis (TNM) stage and metastasis of NPC. Patients with a lower level of miR-212 had significantly decreased rates of overall and disease-free survival. Functional experiments showed that forced expression of miR-212 inhibited the migration and invasion of NPC cells while inhibition of miR-212 increased the migration and invasion of NPC cells. Furthermore, the results of luciferase assay, qRT-PCR and western blotting showed that SOX4 was the direct downstream target of miR-212 in NPC cells. In addition, we further confirmed that miR-212 exerted its inhibitory influence on the migration and invasion of NPC cells by targeting SOX4.
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Carcinoma/prevenção & controle , Movimento Celular , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Nasofaríngeas/prevenção & controle , Fatores de Transcrição SOXC/antagonistas & inibidores , Apoptose , Carcinoma/genética , Carcinoma/secundário , Proliferação de Células , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/secundário , Invasividade Neoplásica , Prognóstico , Células Tumorais CultivadasRESUMO
This study was designed to investigate the effect of laparoscopic gastrectomy on adjuvant chemotherapy in patients with gastric cancer.Patients with gastric cancer who underwent radical gastrectomy at our institution from January 2008 to January 2015 with R0 resection, as determined by a pathological examination, were included in this study. According to the surgical approach, patients were divided into the laparoscopic gastrectomy (LG) group and open gastrectomy (OG) group. Short-term and long-term outcomes were compared between the 2 groups.Of the 206 patients enrolled in the study, 114 patients were included in the LG group and 92 patients were included in the OG group. There was no significant difference in patients' general data, including age, sex, medical comorbidities, and pathological staging, between the 2 groups. However, patients in the LG group had less intraoperative blood loss, fewer postoperative complications, and a shorter hospital stay compared with patients in the OG group. There was no significant difference in the start time of adjuvant chemotherapy between the groups. However, compared with OG, LG had the following advantages: patients received more cycles of adjuvant chemotherapy, more patients received a full dose of on-schedule adjuvant chemotherapy, and more patients completed ≥75% of the planned dose. Long-term survival and disease-free survival rates were higher in the LG than in the OG.In summary, LG can improve compliance with adjuvant chemotherapy and long-term outcomes in patients with gastric cancer.
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Gastrectomia , Laparoscopia , Cooperação do Paciente , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Comorbidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The Axl receptor tyrosine kinase has been demonstrated to be elevated and activated in many human cancers including liver, lung, breast, and pancreatic cancer. Its high expression has been considered as a cancer biomarker for predicting poor prognosis and increased invasiveness/metastasis. OBJECTIVES: The aim of the study was to investigate the clinical significance of Axl in nasopharyngeal carcinoma (NPC) and its role in cell migration and invasion. MATERIAL AND METHODS: We detected Axl expression in 86 collected NPC tissues and 20 collected normal nasopharyngeal epithelial tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical staining. Axl was knocked down by a specific shRNA in NPC cell lines, 5-8F and 6-10B. Transwell assays were used to determine NPC cell migration and invasion. RESULTS: The expressions of Axl mRNA and protein in NPC tissues were significantly higher than those in normal nasopharyngeal epithelial tissues (p < 0.05, respectively). The positive expression of Axl was significantly correlated with distant metastasis and high TNM stage in NPC (p < 0.05, respectively). Furthermore, Axl positive expression was correlated with a worse overall survival of NPC patients (p < 0.05). Multivariate Cox repression analysis indicated that Axl was an independent factor for predicting overall survival of NPC patients (p < 0.05). In vitro studies found that Axl knockdown significantly reduced the number of migrated and invaded 5-8F and 6-10B cells (p < 0.05, respectively). CONCLUSIONS: The positive expression of Axl is correlated with the poor clinicopathological features in NPC. Furthermore, Axl is an independent prognostic marker for predicting overall survival of NPC patients. Functionally, Axl may facilitate tumour progression by promoting NPC cell migration and invasion.
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Biomarcadores Tumorais/genética , Movimento Celular/genética , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Adulto , Biomarcadores Tumorais/metabolismo , Western Blotting/métodos , Western Blotting/estatística & dados numéricos , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/estatística & dados numéricos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , Receptores Proteína Tirosina Quinases/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos , Receptor Tirosina Quinase AxlRESUMO
Neuroendocrine carcinoma and adenocarcinoma existing in the stomach simultaneously is extremely rare. This report presents a 65-year-old male patient who was diagnosed with three types of malignant tumors in the stomach, neuroendocrine carcinoma (NEC), moderately differentiated adenocarcinoma and mucinous adenocarcinoma. In addition, the NEC and moderately differentiated adenocarcinoma existed in the same lesion and, therefore, was referred to as a mixed adenocarcinoma - NEC tumor. The patient underwent laparoscopic-assisted D2 radical total gastrectomy, Roux-en-Y esophagus-jejunum anastomosis and received FOLFOX chemotherapy for six cycles 3 weeks after surgery. Follow-up determined that the patient survived and was tumor-free 12 months after surgery. In conclusion, radical surgery combined with chemotherapy can effectively improve the prognosis of patients with these three specific tumor types simultaneously in the stomach.
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OBJECTIVE: To study the function of lymphangiogenesis and the expression of Cathepsin D (Cath-D) in laryngeal carcinoma metabasis and clinical pathology character. METHOD: The expression of Cath-D were detected in 76 laryngeal carcinoma with immunohistochemistry (SP method). Podoplanin was used as the marker of lympgatic vessel endotheliocytes to label lympgatic vessel in 76 laryngeal carcinoma,lymphatic microvessel density were measured,and the paraneoplastic tissues was used as control group. RESULT: The positive rate of Cath-D in paraneoplastic tissue, laryngeal carcinoma and in pathology classification, in clinical stage, in cervicale lymphonode metastasis negative and positive group were significantly different. However, there had no difference between the positive rate of Cath-D in the age specific and clinical classification. c) The lymphatic microvessel density in paraneoplastic tissue, laryngeal carcinoma and clinical stage, in glottic carcinoma and supraglottic carcinoma, in cervical lymphonode metastasis negative and positive group were significantly different; but there had no difference in age-specific and pathology classification. CONCLUSION: (1) The high expression of lymphatic microvessel density and the increasing expression of Cath-D could promote cervical lymphonode metastasis in aryngeal carcinoma. (2) There had a correlation between the high expression of lymphangiogenesis and Cath-D in laryngeal carcinoma, and had cooperation in aryngeal carcinoma lymphonode metastasis.
Assuntos
Carcinoma/metabolismo , Carcinoma/fisiopatologia , Catepsina D/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/fisiopatologia , Linfangiogênese/fisiologia , Biomarcadores Tumorais/metabolismo , Carcinoma/patologia , Feminino , Glote , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/patologia , Metástase Linfática , Vasos Linfáticos/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismoRESUMO
OBJECTIVE: To study the different surgical approach for the resection of tumors in the anterior skull base and to introduce an approach of the frontal mid-line incision with the nasal pyramid over-turned downward. METHOD: A review of 10 tumors in the anterior skull base employed unlike operative approach was presented. Of the 10 cases, 6 cases were benign tumors and 4 cases were malignant tumors. Two cases underwent the combined craniofacial approach, 3 cases the subfrontal approach, 3 cases the lateral rhinotomy approach, 2 cases the approach of the frontal mid-line incision with the nasal pyramid over-turned downward. RESULT: All tumors were totally resected. All patients were followed up from 1 to 5 years. In the benign tumors group, 6 cases achieved good results and no recurrence. Of the 4 cases with malignant tumors, 1 cases were followed up 1 year and is alive, 2 cases survived after 3 years and 1 case died after 5 years. Three cases died from local recurrence or invaded intra-cranial. CONCLUSION: According to the site, range and pathology of the skull base tumors, the best operative approach should been selected. The approach of the frontal mid-line incision with the nasal pyramid over-turned downward is closer to tumor and easy to repair duramater, has fine exposure of the anterior skull base, minimal retraction of the frontal lobe, and has better clinically worthy.
Assuntos
Neoplasias da Base do Crânio/cirurgia , Base do Crânio/cirurgia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Testa/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Nariz/cirurgiaRESUMO
OBJECTIVE: To evaluate the results of supracricoid partial laryngectomy with laryngoplasty in treating laryngeal cancer and reconstructing its functions. METHODS: One hundred and fifty-nine patients receiving subtotal laryngectomy from 1993 to 1999 were analysed. 4 kinds of operations were performed for them. 46 cases underwent supracricoid partial laryngectomy with the reconstruction of laryngeal function by pedicled flaps. RESULTS: Among the 46 cases receiving supracricoid partiallaryngectomy with laryngoplasty, aspiration did not occur in 40 cases. The decannulation rate was 91.3%, 3, 5 year survival rates were 84.8%, 75%. 41 cases resumed enjoyed satisfactory phonation. CONCLUSION: This form of laryngeal reconstruction in supraericoid partial laryngectomy with laryngoplasty is helpful to restore laryngeal function. It can prevent aspiration and improve the decannulation rate as well as the quality of life in partial laryngectomy patients.