RESUMEN
In the current study, via utilizing H5L (H5L = 2,4-di(3',5'-dicarboxylphenyl)benzoic acid), the symmetrical rigid polycarboxylic acid ligand with V-shape geometry, two new coordination polymers containing Cu(II) and Co(II) have been produced, and their chemical formulae respectively are {[Co5(L)2(H2O)12]·6H2O} n (1) and {[H2N(Me)2][Cu2(L)(H2O)]·DMF·H2O} n (2), leading to a variety kinds of coordination patterns of H5L and multifunctional skeletons. Their inhibitory activity on the insulin resistance of colon cancer patients was assessed. In addition, the detailed mechanism of the compound was also investigated. Firstly, the detection of enzyme-linked immunosorbent assay was carried out and the Tumor Necrosis Factor-α (TNF-α) level and the Interleukin-1ß (IL-1ß) level was detected. Then, the glucose concentration was determined with blood glucose meter. Next, the insulin receptor expression levels of ß cells were determined with the real time reverse transcription-polymerase chain reaction assay. Ultimately, the cytotoxicity of compounds 1 and 2 was determined with Cell Counting Kit-8 assay.
Asunto(s)
Neoplasias del Colon/metabolismo , Complejos de Coordinación/farmacología , Hipoglucemiantes/farmacología , Resistencia a la Insulina/fisiología , Polímeros/farmacología , Glucemia/metabolismo , Cobalto/química , Cobalto/toxicidad , Neoplasias del Colon/sangre , Neoplasias del Colon/fisiopatología , Complejos de Coordinación/química , Complejos de Coordinación/toxicidad , Cobre/química , Cobre/toxicidad , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/toxicidad , Interleucina-1beta/metabolismo , Polímeros/química , Polímeros/toxicidad , Receptor de Insulina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: This study aimed to evaluate the expression of chemokine-like factor superfamily 6 (CMTM6) and programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) in oral squamous cell carcinoma (OSCC) and to further explore its clinical significance in OSCC. STUDY DESIGN: Samples of 44 OSCC and paracancerous tissues were investigated. We estimated the expression of the 3 proteins by immunohistochemistry and further detected mRNA expression by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Immunohistochemistry results demonstrated that the positive expression of CMTM6 and PD-1/PD-L1 in OSCC tissues was significantly higher than that in paracancerous tissues. Statistical significance was found between the 2 groups (all P < .05). Moreover, PD-L1 expression was related to OSCC clinical stage and lymph node metastasis (P < .05). The qRT-PCR results confirmed that the relative expression of CMTM6 and PD-1/PD-L1 mRNA in OSCC tissues was significantly higher than that in paracancerous tissues (all P < .05), and Spearman rank correlation showed that there was a significant relationship between mRNA and protein expression (all P < .05). CONCLUSIONS: CMTM6 and PD-1/PD-L1 were upregulated in OSCC, and CMTM6 may play a synergistic role with PD-1/PD-L1 in the immune pathway. Therefore, we believe that CMTM6 and PD-1/PD-L1 will become checkpoints for immunotherapy of OSCC.
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Antígeno B7-H1/genética , Proteínas con Dominio MARVEL/genética , Neoplasias de la Boca , Proteínas de la Mielina/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Neoplasias de la Boca/genética , Receptor de Muerte Celular Programada 1 , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignancy in the world. DNA cytosine-5-methyltransferase 1 (DNMT1) play key roles in carcinogenesis and regulation of the immune micro-environment, but the gene expression and the role of DNMT1 in HNSCC is unknown. In this study, we utilized online tools and databases for pan-cancer and HNSCC analysis of DNMT1 expression and its association with clinical cancer characteristics. We also identified genes that positively and negatively correlated with DNMT1 expression and identified eight hub genes based on protein-protein interaction (PPI) network analysis. Enrichment analyses were performed to explore the biological functions related with of DNMT1. The Tumor Immune Estimation Resource (TIMER) database was performed to explore the relationship between DNMT1 expression and immune-cell infiltration. We demonstrated that DNMT1 gene expression was upregulated in HNSCC and associated with poor prognosis. Based on analysis of the eight hub genes, we determined that DNMT1 may be involved in cell cycle, proliferation and metabolic related pathways. We also found that significant difference of B cells infiltration based on TP 53 mutation. These findings suggest that DNMT1 related epigenetic alterations have close relationship with HNSCC progression, and DNMT1 could be a novel diagnostic biomarker and a promising therapeutic target for HNSCC.
Asunto(s)
Biología Computacional , ADN (Citosina-5-)-Metiltransferasa 1/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Perfilación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Mutación/genética , Pronóstico , Mapas de Interacción de Proteínas/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
PURPOSE: To investigate the distribution of oral candida species in head and neck cancer (HNC) patients treated with radiation therapy, and provide the basis for planning of clinical preventive measures. METHODS: Saliva was sampled from 60 HNC patients before, during and after radiation. Concomitantly, 60 healthy individuals whose age and sex matched that of the patient group were selected as control group. Oral candida carriages were quantitatively detected and the different candida species were identified by multiple measures such as CHROMagar candida culture medium and API 20C AUX yeast identification system. Then the differences between the two groups in terms of the candida detection rate and the distribution of each species of candida were analyzed with SPSS 17.0 software package. RESULTS: Xerostomia and dysphagia was found in 54 HNC patients during radiotherapy, radiation-induced oral mucotitis(RIOM) was found in 50 HNC patients,and oral candidiasis was found in 18 HNC patients; In radiation group, the detection rate of candida colonization during radiation was 56.7%, 63.3% postradiation, which showed significant differences compared with pre-radiation (X² =18.320,P<0.001 ); Among the 54 identified clinical isolates, candida albicans (n=42) was the most frequent, followed by candida parapsilosis (n=6), candida tropicalis (n=4) and candida glabrata (n=2). In radiation group, the oral candida pathogens detection rate was 30%, and candida colonization was 46.7%. CONCLUSIONS: The oral candida colonization rate was significantly higher in HNC patients after radiotherapy, which indicated that the candida infection may be closely related to RIOM.
Asunto(s)
Candida , Candidiasis Bucal , Neoplasias de Cabeza y Cuello/radioterapia , Candida albicans , Estudios de Casos y Controles , Humanos , SalivaRESUMEN
We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
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Pueblo Asiatico/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Alelos , Estudios de Casos y Controles , Carcinoma de Células Escamosas de Esófago , Femenino , Sitios Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , RiesgoRESUMEN
Oral lichen planus (OLP) is a T cell-mediated autoimmune disease of oral mucosa, in which T helper 1 (Th1) cells are greatly involved. Chemokine CCL5 is required for T cells infiltration and activation. CCR5, one of its receptors, specifically expressed on Th1 cells among CD4(+) T cells, can be up-regulated by Th1 cytokines like interleukin2 (IL-2) and interferon-gamma (IFN-γ), and down-regulated by Th2 cytokines like IL-4. The present study aimed to determine whether CCL5 and CCR5 had effects on the immune response of OLP. We analyzed the proportion of CCR5(+)CD4(+) T cells in CD4(+) T cells using flow cytometry and the serum levels of CCL5, IL-2, IFN-γ, and IL-4 with ELISA. MicroRNA-125a (miR-125a), a blocker of CCL5, was examined with RT-PCR. The results showed both the serum CCL5 and the percentage of CCR5(+)CD4(+) T cells elevated in OLP patients. Serum IL-2 and IFN-γ increased in OLP patients, but IL-4 decreased. MiR-125a was down-regulated in OLP patients, and there was a negative correlation between miR-125a content and the OLP severity which was measured with a RAE (reticular, atrophic and erosive lesion) scoring system. In conclusion, increasing CCl5/CCR5 might participate in the immune response of OLP. Th1-type cytokines environment presented in OLP probably performed as a magnifier for the CCR5. Moreover, miR-125a might be a candidate biomarker to estimate the severity of OLP.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Quimiocina CCL5/metabolismo , Liquen Plano Oral/inmunología , Receptores CCR5/metabolismo , Adulto , Anciano , Femenino , Humanos , Interferón gamma/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Liquen Plano Oral/sangre , Liquen Plano Oral/genética , Liquen Plano Oral/patología , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Transducción de Señal , Adulto JovenRESUMEN
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.