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OBJECTIVES: The study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection. METHODS: Differentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential. RESULTS: Upregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis. CONCLUSIONS: ECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.
Assuntos
Biomarcadores Tumorais , Neoplasias do Endométrio , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Mapas de Interação de Proteínas/genética , Regulação para Cima , Perfilação da Expressão GênicaRESUMO
BACKGROUND: The dynamic interaction between cancer cells and tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is an active barrier to the effector arm of the antitumour immune response. Cancer-secreted exosomes are emerging mediators of this cancer-stromal cross-talk in the TME; however, the mechanisms underlying this interaction remain unclear. METHODS: Exosomes were isolated with ExoQuick exosome precipitation solution. The polarizing effect of TAMs was evaluated by flow cytometry, western blot analysis, immunofluorescence staining and in vitro phagocytosis assays. Clinical cervical cancer specimens and an in vivo xenograft model were also employed. RESULTS: Our previous study showed that hypoxia increased the expression of ZEB1 in cervical squamous cell carcinoma (CSCC) cells, which resulted in increased infiltration of TAMs. Here, we found that hypoxia-induced ZEB1 expression is closely correlated with CD47-SIRPα axis activity in CSCC, which enables cancer cells to evade phagocytosis by macrophages and promotes tumour progression. ZEB1 was found to directly activate the transcription of the CD47 gene in hypoxic CSCC cells. We further showed that endogenous ZEB1 was characteristically enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes to promote SIRPα+ TAM polarization. Intriguingly, exosomal ZEB1 retained transcriptional activity and reprogrammed SIRPα+ TAMs via activation of the STAT3 signalling pathway in vitro and in vivo. STAT3 inhibition reduced the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increased the phagocytosis of CSCC cells by macrophages via decreasing CD47 and SIRPα expression. CONCLUSIONS: Our results suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPα axis. ZEB1-targeted therapy in combination with CD47-SIRPα checkpoint immunotherapy may improve the outcomes of CSCC patients in part by disinhibiting innate immunity.
Assuntos
Carcinoma de Células Escamosas , Evasão Tumoral , Neoplasias do Colo do Útero , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Feminino , Humanos , Antígeno CD47 , Exossomos , Evasão da Resposta Imune , Microambiente Tumoral , Neoplasias do Colo do Útero/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismoRESUMO
In this study, ε-polylysine and calcium phosphate precipitation (CPP) methods were employed to induce antibacterial effects and dentin tubule occlusion. Antibacterial effects of ε-polylysine were evaluated with broth dilution assay against P. gingivalis. CPP solution from MCPM, DCPD, and TTCP was prepared. Four concentrations of ε-polylysine(ε-PL) solutions (0.125%, 0.25%, 0.5%, 1%) were prepared. Dentin discs were prepared from recently extracted human third molars. Dentin discs were incubated with P. gingivalis (ATCC 33277) bacterial suspension (ca. 105 bacteria) containing Brain Heart Infusion medium supplemented with 0.1 g/mL Vitamin K, 0.5 mg/mL hemin, 0.4 g/mL L-cysteine in anaerobic jars (37 °C) for 7 days to allow for biofilm formation. P. g-infected dentin specimens were randomly divided into four groups: CPP + 0.125% ε-PL, CPP + 0.25% ε-PL, CPP + 0.5% ε-PL, CPP + 1% ε-PL. On each dentin specimen, CPP solution was applied followed by polylysine solution with microbrush and immersed in artificial saliva. Precipitate formation, antibacterial effects, and occlusion of dentinal tubules were characterized in vitro over up to 72 h using scanning electron microscopy. ε-PL showed 34.97% to 61.19% growth inhibition levels against P. gingivalis (P. g) after 24 h of incubation. On P. g-infected dentin specimens, DCPD + 0.25% ε-PL, and DCPD + 0.5% ε-PL groups showed complete bacterial inhibition and 78.6% and 98.1% dentin tubule occlusion, respectively (p < 0.001). The longitudinal analysis on fractured dentin samples in DCPD and TTCP groups revealed deeply penetrated hydroxyapatite-like crystal formations in dentinal tubules after 72 h of incubation in artificial saliva.
Assuntos
Antibacterianos/farmacologia , Fosfatos de Cálcio/farmacologia , Dentina/química , Polilisina/farmacologia , Antibacterianos/química , Fosfatos de Cálcio/química , Dentina/metabolismo , Sensibilidade da Dentina/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Polilisina/química , Análise Espectral , Propriedades de SuperfícieRESUMO
Antimicrobials are important adjuncts in the treatment of caries and periodontitis. However, increased bacterial resistance and hypersensitivity reactions to commonly used antimicrobials have led to an increasing demand for safe and natural substances. The objective of this study was to investigate the antibacterial effects of ε-polylysine against oral pathogens Streptococcus mutans and Porphyromonas gingivalis. Broth dilution assay, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) analyses were performed to explore the antibacterial effect of ε-polylysine against S. mutans strain ATCC25175 and P. gingivalis strain ATCC332277. For the test solution, ε-polylysine was added to the bacterial suspension to prepare 0.125%, 0.25%, 0.5% and 1% ε-polylysine solutions diluted in broth medium. All four concentrations demonstrated complete inhibition of S. mutans and significantly reduced viable cell counts of P. gingivalis after 24 h. From starting inoculum of 9.15 log CFU/mL, P. gingivalis cell counts reduced to 4.01 log CFU/mL in the 0.125% ε-polylysine treatment group. SEM, CLSM, and the LIVE/DEAD bacterial assay of ε-polylysine application on P. gingivalis biofilm-dentin specimens revealed bacterial cell membrane disruption and irregular cell morphologies. The results indicated satisfactory antibacterial efficacy of ε-polylysine against P. gingivalis and S. mutans in liquid medium and as an application on biofilm-dentin specimens.
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Anion- and solvent-induced single-crystal-to-single-crystal transformation within an iron(II) triazole system has been generated from {[Fe(TPPT)2Cl2]·CHCl3} n (1a) to [Fe(TPPT)(C2O4)0.5Cl(H2O)] n (1b). Luminescence studies indicated that the resultant 1b can be considered as a promising luminescent probe for CrO42- and cyano molecules.
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BACKGROUND: Extraneural metastasis of oligodendroglioma is extremely rare and is diagnosed primarily by biopsy or autopsy and very occasionally by fine needle cytologic examination. We report a case of metastatic oligodendroglioma diagnosed by cytologic examination of a pleural effusion. Such a diagnosis has not been reported before. CASE: A 64-year-old woman developed anemia and bilateral pleural effusion 7 years after an operation for an oligodendroglioma over the left frontal lobe. Cytologic examination of the pleural effusion showed aggregates of atypical polygonal cells containing round, hyperchromatic nuclei and scanty, granular cytoplasm in Liu's and Papanicolaou stain and cell blocks. Immunohistochemical staining of the tumor cells revealed a positive reaction for antibodies to glial fibrillary acidic protein, S-100 and Olig2. Pleural biopsy confirmed the cytologic diagnosis of pleural effusion. A pathologic fracture of the right humeral and femoral bones was noted 1 month later, and the specimen also showed infiltrating oligodendroglioma cells in bone tissue. CONCLUSION: To the best of our knowledge, this is the first metastatic oligodendroglioma diagnosed by pleural cytology. Fine needle cytology can provide a reliable and rapid way to detect an extracranial metastatic oligodendroglioma in different organs.