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β-Thalassemia is characterized by ineffective erythropoiesis leading to chronic anemia. Thus, increased iron absorption from the duodenum and via blood transfusions is required to maintain normal blood hemoglobin (Hb) levels and iron chelators in the removal of excessive iron. Certain agents are also needed for the improvement of stress erythropoiesis and iron dysregulation. Green tea extract (GTE), which is rich in epigallocatechin-3-gallate (EGCG), is known to possess radical scavenging and iron-chelating activities. We aimed to assess the effects of green tea extract on erythroid regulators, iron mobilization and anti–lipid peroxidation in the liver, spleen, and kidneys of iron-loaded β-globin gene knockout thalassemic (BKO) mice. Our results indicate that treatments of green tea extract and/or deferiprone (DFP) diminished levels of plasma erythropoietin (EPO) and erythroferrone (ERFE), and consistently suppressed kidney Epo and spleen Erfe mRNA expressions (p < .05) in iron- loaded BKO mice when compared with untreated mice. Coincidently, the treatments decreased plasma ferritin (Ft) levels, iron content levels in the liver (p < .05), spleen (p < .05), and kidney tissues of iron–loaded BKO mice. Furthermore, lipid-peroxidation products in the tissues and plasma were also decreased when compared with untreated mice. This is the first evidence of the orchestral role of green tea extract abundant with epigallocatechin-3-gallate in improving ineffective erythropoiesis, iron dysregulation and oxidative stress in iron-overloaded β-thalassemic mice.

Results: The average number of dissected LNs was 22.7±12.8. Tumor recurrence was found in 51.3% and overall mortality was 43.3%. The number of dissected LNs was a prognostic factor for tumor recurrence [HR 0.98, 95% confidence interval (CI): 0.96-0.99]. There was a significant difference at the cut-pointed value of 11 dissected LNs for tumor recurrence (HR 2.22, 95% CI: 1.26-3.92). Dissection less than 11 nodes and less than 5 stations indicated a poor prognostic factor for tumor recurrence: for 3-4 stations (HR 3.01, 95% CI: 1.22-7.42) and for 1-2 stations (HR 1.96, 95% CI: 1.04-3.72). The positivity of dissected LNs was also a prognostic factor for tumor recurrence and overall mortality (HR 1.01, 95% CI: 1.01-1.02 and HR 1.01, 95% CI: 1.01-1.03, respectively).Conclusions: Eleven or more LN dissection with at least 5 stations influenced recurrent-free survival.Systematic LN dissection (SLND) should be performed not only to identify the positivity of dissected LNs but also to determine an accurate tumor nodal stage. A larger cohort should be further conducted to support these findings.

The main risk factor for esophageal dysplasia and adenocarcinoma (DAC) is Barrett's esophagus (BE), characterized by intestinal metaplasia. The critical genomic mechanisms that lead to progression of nondysplastic BE to DAC remain poorly understood and require analyses of longitudinal patient cohorts and high‐resolution assays. We tested BE tissues from 74 patients, including 42 nonprogressors from two separate groups of 21 patients each and 32 progressors (16 in a longitudinal cohort before DAC/preprogression‐BE and 16 with temporally concurrent but spatially separate DAC/concurrent‐BE). We interrogated genome‐wide somatic copy number alterations (SCNAs) at the exon level with high‐resolution SNP arrays in DNA from formalin‐fixed samples histologically confirmed as nondysplastic BE. The most frequent abnormalities were SCNAs involving FHIT exon 5, CDKN2A/B or both in 88% longitudinal BE progressors to DAC vs. 24% in both nonprogressor groups (p = 0.0004). Deletions in other genomic regions were found in 56% of preprogression‐BE but only in one nonprogressor‐BE (p = 0.0004). SCNAs involving FHIT exon 5 and CDKN2A/B were also frequently detected in BE temporally concurrent with DAC. TP53 losses were detected in concurrent‐BE but not earlier in preprogression‐BE tissues of patients who developed DAC. CDKN2A/p16 immunohistochemistry showed significant loss of expression in BE of progressors vs. nonprogressors, supporting the genomic data. Our data suggest a role for CDKN2A/B and FHIT in early progression of BE to dysplasia and adenocarcinoma that warrants future mechanistic research. Alterations in CDKN2A/B and FHIT by high‐resolution assays may serve as biomarkers of increased risk of progression to DAC when detected in BE tissues.