We introduce Twist1 and MAML1 as new molecular markers of advanced tumor, which determine the characteristics and aggressive behavior of ESCC. Along with the emerging evidence of their role in different cellular processes and aberrations in various cancers, they are suggested as potentially interesting therapeutic targets to reverse a broad spectrum of functional aberrations that promote ESCC development.
Wnt signaling is an important evolutionary conserved pathway that is not only involved in determination of cellular development, self-renewal, and fate, but also has significant roles in tumor development and progression. Deregulation of the Wnt/β-catenin signaling pathway and aberrant expression of its components is commonly observed in solid tumors. Such aberrant regulation of Wnt signaling is commonly related to either malfunction of its components or crosstalk with other cellular processes such as the epidermal growth factor receptor (EGFR) signaling cascade. Therefore, identification of the roles of major involved components may be useful to identify new therapeutic targets for cancer treatment. In this study, we assessed EGFR and PYGO2 mRNA expression in tumors and margin normal tissues from 55 esophageal squamous cell carcinoma (ESCC) patients using real-time qRT-PCR, and evaluated clinicopathology relative to the two genes' expression levels. Significant PYGO2 and EGFR overexpression was observed in 30.9 % (P = 0.017) and 38.2 % (P = 0.006) of tumors, respectively. PYGO2 and EGFR expression were significantly associated not only with each other (P < 0.001), but also with tumor staging and depth (P < 0.001). Furthermore, PYGO2 expression was significantly correlated with the tumor grade (P = 0.043) and size (P = 0.023). We identify PYGO2 as a new molecular marker of invasive tumors, introducing its probable oncogenic role in ESCC progression and aggressiveness. In line with other reports, we also illustrate the oncogenic function of EGFR in the development of ESCC through advance stages. We also observed a significant correlation between PYGO2 and EGFR in ESCC tumors, which reveals a mutual convergent influence of these factors in tumor progression and development. Considering aberrant expression, mutual positive feedback, and the significant clinical relevance of these genes in ESCC, we introduce them as appropriate therapeutic targets in adjuvant therapy of ESCC.
The aim of this study was to determine the age of appearance of secondary sexual characteristics in Iranian girls living in Tehran. A cross-sectional study was conducted between 2003 and 2004 on 1420 6-17-year-old females in different parts of Tehran. Data were collected on the basis of a multistage probability sampling. Secondary sexual characteristics were evaluated by inspection and palpation, and were recorded according to Tanner staging. The subjects were asked about the occurrence of menarche and the age of its onset. Generalized additive logistic modelling was used for the analysis of data. The median age (percentile 10-percentile 90) of Tanner 2 of breast development (B2) and Tanner 2 of pubic hair growth (P2) among 1136 girls was 9.74 years (8.23-11.94) and 10.49 years (8.86-12.17), respectively. The ages of the 2.5 percentile for B2 and P2 were 7.42 and 7.03 years, respectively, so the onset of puberty at < 7 years and 5 months is considered precocious in this population. The median age of menarche in 399 girls was 12.68 years (11.27-15.96).
BACKGROUND: Block of programmed cell death protein 1 (PD-1) interaction with its ligand, PD-L1, enhances anti-tumor activity. OBJECTIVES: We aimed to assess the association between PD-L1 expression in tumor cells and CD8+ tumor infiltrating T cells (TILs) as well as soluble (s)PD-L1 serum levels in patients with triple negative breast cancer (TNBC) compared to triple positive (TPBC). METHODS: A total of 113 tumor sections and 133 serum samples were available from 144 patients with breast cancer (72 TNBC and 72 TPBC). Dual immunohistochemistry staining was applied to determine differential PD-L1 expression in tumor cells and CD8+ TILs. Soluble PD-L1 serum levels were also evaluated in patients compared to 40 healthy women by ELISA method. RESULTS: Despite TPBC patients which were mostly grades 1/2, TNBC patients were grade 3 (72% versus 66.7%, P < 0.001). Most of the TNBC patients were stages I/II, whereas most of the TPBC patients were stages III/IV (57.3% versus 68.3%,P = 0.005). There was no difference in tumor size and metastasis between TNBC and TPBC patients, although the number of involved lymph nodes was significantly more in TPBC patients (P = 0.0012). PD-L1 expression was detected in 11.5% of samples mostly in TNBC subtype and was associated with advanced grades (P = 0.039). There was no relationship between PD-L1 expression and tumor stage. PD-L1 expression in CD8+ TILs was nonsignificantly higher than tumor cells. Serum levels of sPD-L1 showed no difference between patients and healthy women. We found no correlation between PD-L1 expression in tumor lesions and serum levels of sPD-L1 in patients. CONCLUSION: PD-L1 expression was more detected in our patients with TNBC. It seems that, these patients who are resistant to standard chemotherapy regimens may get benefit from PD-L1 inhibition therapy and because of its low serum levels, sPD-L1 cannot interfere with this therapy.
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