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Objective:To investigate the changes of inflammation and immune function in children with chronic tonsillitis after tonsillotomy. Methods:Prospectively collected 60 children with obstructive sleep apnea ï¼OSAï¼ diagnosed as chronic tonsillitis with adenoids and tonsillar hypertrophy from January to June 2021. Two groups were divided, the experimental group ï¼n=30ï¼ underwent bilateral partial tonsillectomy + adenoidectomy by hypothermia plasma ablation, and the control group ï¼n=30ï¼ underwent adenoidectomy by using the same hypothermia plasma ablation method. The number of tonsillitis attacks before surgery and within one year after surgery was recorded, and the serum immunoglobulin IgM, IgG, IgA, complement C3 and complement C4 levels before operation, one month and three months after operation were measured. Results:The number of tonsillitis attacks in the experimental group and the control group at one year after surgery was lower than that before surgeryï¼P<0.05ï¼; The number of inflammatory attacks in the experimental group was ï¼0.50±0.63ï¼ times/year, which was lower than that of ï¼1.33±0.80ï¼ times/year in the control group. There was no significant difference in the five immunization results of the two groups at one month and three months after operation compared with before operation, and there was also no significant difference between the experimental and the control groups. Conclusion:Partial tonsillectomy can be applied to children with chronic tonsillitis, which can effectively reduce the number of tonsillitis attacks and has no effect on the immune function of children.
Assuntos
Hipotermia , Tonsilectomia , Tonsilite , Criança , Humanos , Tonsilectomia/métodos , Tonsilite/cirurgia , Adenoidectomia , Tonsila Palatina/cirurgia , Inflamação , Doença Crônica , ImunidadeRESUMO
Recurrent/metastatic nasopharyngeal carcinoma (NPC) is known for having a poor prognosis due to its unfavorable response to chemoradiotherapy. However, the specific processes involved remain poorly understood. This study focused on the cisplatin-resistance mechanism in NPC to help understand the occurrence of advanced NPC and aims to explore the potential therapeutic target for cisplatin-resistant NPC. Two cisplatin-resistant NPC cell lines, HNE-1/DDP and CNE-2/DDP, were established and the differentially expressed genes (DEGs) between parental and cisplatin-resistance cell lines, filtering from high-throughput sequencing results, were analyzed. Next, the effects of IAP-1 on cisplatin-resistant nasopharyngeal cancer cell proliferation, apoptosis, drug resistance and associated cell signaling were evaluated in vitro and in vitro. From our bioinformatic results, more than 15,000 differentially expressed genes (DEGs) were found between parental and resistant cell lines. Nine related DEGs were found in the classic platinum resistance pathway, three of which (ATM, IAP-1, and IAP-2) also appeared in the top five differentially expressed pathways, with elevated IAP-1 showing the highest fold change. Further studies revealed that high IAP-1 expression can lead to an increased cisplatin inhibitory concentration and apoptosis inhibition. IAP-1 silencing can induce upregulation of the caspase-3 and enhance the antiproliferation and proapoptotic effects of cisplatin. Clinical data also showed that IAP-1 overexpression was associated with a worse survival status. In summary, in vitro and in vivo experiments demonstrated that IAP-1 plays a vital role in cisplatin resistance by regulating caspase induced apoptosis and serve as a potential novel therapeutic target and a prognostic indicator for advanced NPC.
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Nasopharyngeal carcinoma (NPC) is a common malignant tumor and a major cause of mortality and morbidity in southern China. However, the mechanism is still elusive. Here, we focused on studying the role of squalene epoxidase (SQLE), a key enzyme of cholesterol biosynthesis, in the progression of NPC. Clinical study revealed that SQLE expression was significantly upregulated in NPC tissues compared to normal tissues from mRNA level and patients with high expression of SQLE showed a poor prognosis. In vitro experiments showed that SQLE overexpression led to a significant proliferation of cells whereas SQLE knockdown showed an opposite result. In vivo studies also showed that SQLE promoted tumor growth in nude mice. Further study revealed that SQLE promoted NPC proliferation by cholesteryl ester accumulation instead of cholesterol. Mechanism studies indicated that cholesteryl ester promoted NPC cell proliferation by activating the PI3K/AKT pathway and inhibition of this pathway in SQLE-overexpressed or cholesteryl ester-treated cells resulted in a significant reduction of NPC cell proliferation. These results indicate that the oncogenic effect of SQLE in NPC mainly resulted from cholesteryl ester accumulation and PI3K/AKT is a promising target for NPC with SQLE overexpression.
Assuntos
Ésteres do Colesterol/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Esqualeno Mono-Oxigenase/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/genética , Biomarcadores Tumorais , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Nus , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Prognóstico , Esqualeno Mono-Oxigenase/antagonistas & inibidores , Esqualeno Mono-Oxigenase/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
As chemo-radiotherapy continues to increase the lifespan of patients with nasopharyngeal carcinoma (NPC), adverse reaction and drug resistance remain two major problems when using cisplatin (CDDP). In this study, we took the lead in designing a dual-mechanism anti-cancer system modified with cell-penetrating peptide on the surface of superparamagnetic iron oxide nanoparticles (SPION) to enhance CDDP delivery efficacy to NPC cells, especially CDDP resistant NPC cells. The combinatorial delivery of CDDP and iron oxide nanoparticles showed an unexpected effect on reversal of CDDP resistance due to the Fenton reaction with an average decrease in the half maximal inhibitory concentration (IC 50) of 85% and 94% in HNE-1/DDP and CNE-2/DDP resistant cells respectively compared to CDDP alone. On this basis, modification with TAT peptide (YGRKKRRQRRR) significantly improved tumor intracellular uptake, devoting to better curative effects and minimized side effects by reducing CDDP therapeutic doses. Furthermore, we specifically labelled CDDP with fluorescence for detection of intracellular nanoparticles uptake and mechanism research through drug tracing. This novel compound provides a promising therapy for reducing chemotherapy side effects and reversing CDDP-resistant nasopharyngeal carcinoma.
Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Nanopartículas de Magnetita/química , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Fragmentos de Peptídeos/química , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacocinética , Cisplatino/farmacologia , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos , HumanosRESUMO
The co-delivery of a drug and a target gene has become a primary strategy in cancer therapy. Based on our previous study, a synthesized starshaped copolymer consisting of ßcyclodextrin (CD) and a poly(Llysine) dendron (PLLD) was used to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP9) small interfering RNA, via CDPLLD/DOC/MMP9 complexes, into mice implanted with HNE1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly used amphiphilic copolymer micelles, the obtained CD derivative may be used directly for a combined delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vivo assays demonstrated that CDPLLD/DOC/MMP9 inhibited HNE1 tumor growth and decreased proliferating cell nuclear antigen expression levels, indicating a potential strategy for NPC therapy. In addition, the distribution of DOC and MMP9 was investigated; CDPLLD/DOC/MMP9 complexes were phagocytized in reticuloendothelial systems, including the liver and spleen, which requires further study. Furthermore, the complexes did not cross the bloodbrain barrier due to their large molecular size, suggesting they may be relatively safe. Additionally, the complexes mediated increased DOC concentrations with prolonged blood circulation and EGFP expression in HNE1 tumors. These results suggest the future potential application of CD-PLLD/DOC/MMP-9 for NPC therapy.