ABSTRACT
Progresses in multimodal treatments have significantly improved the outcomes for childhood cancer. Nonetheless, for about one-third of patients with Ewing sarcoma, rhabdomyosarcoma, or osteosarcoma steady remission has remained intangible. Thus, new biomarkers to improve early diagnosis and the development of precision-targeted medicine remain imperative. Over the last decade, remarkable progress has been made in the basic understanding of miRNAs function and in interpreting the contribution of their dysregulation to cancer development and progression. On this basis, this review focuses on what has been learned about the pivotal roles of miRNAs in the regulation of key genes implicated in childhood sarcomas.
Subject(s)
Bone Neoplasms/metabolism , MicroRNAs/metabolism , Osteosarcoma/metabolism , Rhabdomyosarcoma/metabolism , Sarcoma, Ewing/metabolism , Bone Neoplasms/genetics , Child , Down-Regulation , Humans , Osteosarcoma/genetics , Rhabdomyosarcoma/genetics , Sarcoma, Ewing/genetics , Up-RegulationABSTRACT
DAX1 transcription factor is a key determinant of adrenogonadal development, acting as a repressor of SF1 targets in steroidogenesis. It was recently demonstrated that DAX1 regulates pluripotency and differentiation in murine embryonic stem cells. In this study, we investigated DAX1 expression in adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34 children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30 carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real-time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34) and 24% (17 out of 70) of pediatric and adult ACTs, respectively (χ(2)=10.1, p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5-4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with functional status in ACTs. Interestingly, a positive correlation was observed between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55 for each group separately; p<0.0001). In addition, DAX1 gene expression was significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In conclusion, DAX1 strong protein expression was more frequent in pediatric than in adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs, suggesting that these transcription factors might cooperate in adrenocortical tumorigenesis.
Subject(s)
Adrenal Cortex Neoplasms/metabolism , Carcinogenesis/metabolism , DAX-1 Orphan Nuclear Receptor/metabolism , Steroidogenic Factor 1/metabolism , Adrenal Cortex Neoplasms/genetics , Adrenocortical Adenoma/genetics , Adrenocortical Adenoma/metabolism , Adrenocortical Carcinoma/genetics , Adrenocortical Carcinoma/metabolism , Adult , Carcinogenesis/genetics , Child , Child, Preschool , DAX-1 Orphan Nuclear Receptor/genetics , Female , Gene Expression , Humans , Infant , Male , Middle Aged , Steroidogenic Factor 1/geneticsABSTRACT
OBJECTIVE: The aims of the present study were to investigate the effect of low-intensity laser irradiation on the total number of mast cells as well as the percentage of degranulation in human gingiva. Blood vessel dilation was also evaluated. BACKGROUND DATA: It has been proposed that low-intensity laser irradiation can ameliorate pain, swelling, and inflammation. In periodontal tissue, mast cells may influence either the destructive events or the defense mechanism against periodontal disease via secretion of cytokines and through cellular migration to improve the healing process. Mast cells play an important role in the inflammatory process. METHODS: Twenty patients with gingival enlargement indicated for gingivectomy were selected. Gingival fragments were obtained from each patient and divided into three different groups before surgery. One fragment was removed without any irradiation. The two others were submitted to punctual irradiation with an energy density of 8 J/cm(2) at an output power of 50 mW at 36 Hz for 36 sec before gingivectomy. Nondegranulated and degranulated mast cells were counted in five areas of the gingival fragment connective tissue. Major and minor diameters of the blood vessels were also measured. RESULTS: Both red and infrared radiation promoted a significant increase in mast cell degranulation compared to controls; however, no statistically significant differences (p > 0.05) were observed between the irradiated groups. No significant differences among the groups were observed regarding blood vessel size. CONCLUSION: The results suggests that red and infrared wavelengths promote mast cell degranulation in human gingival tissue, although no dilation of blood vessels was observed. The effects of premature degranulation of mast cells in human tissue and the laser radiation protocol applied in this study encourage further investigations to extend these results into clinical practice.
