RESUMO
In this work, an environmentally friendly strategy was used to synthesize gold nanoparticles (Au NPs) using Olea europaea (olive) fruit. Transmission electron microscopy (TEM), UV-Vis spectroscopy, X-ray diffraction (XRD) and energy-dispersive X-ray (EDX) were used to characterize the physicochemical properties of the synthesized NPs. An Au NPs modified glassy carbon electrode was used to investigate the direct electrochemical oxidation of hydrazine. The suggested hydrazine sensor has good performance, such as a wide linear range (2.5-275 µM), low limit of detection (0.09 µM), notable selectivity and excellent reproducibility (RSD = 2.2%). The in-vitro cytotoxicity of three human cancer cell lines (KATOIII, NCI-N87, and SNU-16) was also explored with various concentrations of Au NPs prepared from olive fruit extract. Bio-synthesized Au NPs were found to have cytotoxic properties against gastric cancer in humans based on MTT assay protocol. The obtained results show that green synthesized Au NPs can be successfully employed in electrochemical sensing and cancer treatment applications.
Assuntos
Nanopartículas Metálicas , Neoplasias Gástricas , Humanos , Nanopartículas Metálicas/química , Ouro/química , Reprodutibilidade dos Testes , HidrazinasRESUMO
PDZ-binding kinase (PBK/TOPK) acts as oncogene in various cancers and correlates with drug response. However, few studies have examined the expression and roles of PBK in colonrectal cancer (CRC). In this study, we found a significant increase in the expression of PBK in CRC tissues and cell lines. While overexpression of PBK promoted cell growth and decreased the toxicity effect of oxaliplation (OXA), targeting PBK with short hairpin RNA (shRNA) or novel PBK inhibitor HI-TOPK-032 effectively suppressed tumor growth and potentiated chemosensitivity in vitro and in vivo. Furthermore, there was a significant inverse correlation between the expressions of miR-216b and PBK. Further found that miR-216b could down-regulate PBK levels by binding to the 3' untranslated region (3'UTR) of PBK. Notably, while miR-216b decreased cell proliferation and enhanced sensitivity of CRC cells to oxaliplation, re-expression of PBK dramatically reversed these events. Collectively, our data indicated that miR-216b may function as a tumor suppressor though regulating PBK expression, which provided promising targets and possible therapeutic strategies for CRC treatment.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , MicroRNAs/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno/biossíntese , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Neoplasias Colorretais/genética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: The rapid adoption of next-generation sequencing in clinical oncology has enabled detection of molecular biomarkers which are shared between multiple tumour types. Intra-tumour heterogeneity is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the tumour-related copy number variants (CNVs), as key regulators of cancer origination, development, and progression, across various types of cancers are poorly understood. METHODS: We performed pan-cancer CNV analysis of cancer-related genes in 15 types of cancers including 1438 cancerous patients by next-generation sequencing using a commercially available pan-cancer panel (Onco PanScan™). Downstream bioinformatics analysis was performed in order to detect CNVs, cluster analysis of the found CNVs, and comparison of the frequency of gained CNVs between different types of cancers. LASSO analysis was used for identification of the most important CNVs. RESULTS: We also identified 523 CNVs among which 16 CNVs were common while 22 CNVs were caner-specific CNVs. Meanwhile, FAM58A was most commonly found in all studied cancers in this study and significant differences were found in FAM58A between female and male patients (p = .001). Common CNVs, such as FOXA1, NFKBIA, HEY1, MECOM, CHD7, AGO2, were mutated in 6.79%, 8.45%, 7.51%, 6.43%, 7.59%, 8.16% of tumours, while most of these mutations have proven roles in positive regulation of transcription from RNA polymerase II promoter. 11 features including sex, DIS3, EPHB1, ERBB2, FLT1, HCK, KEAP1, MYD88, PARP3, TBX3, and TOP2A were found as the key features for classification of cancers using CNVs. CONCLUSION: The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.