Advances in the mechanism of Tbx2 regulation in embryonic cardiac development / 国际儿科学杂志

Embryonic cardiogenesis requires precise expression of various genes.This process involves a complex model of gene regulation,in which any deviation will lead to the occurrence of heart defects.Expression of Tbx2 in different species is ultimately confined to the atrioventricular canal in the non-ventricular myocardium,suggesting that the temporal and spatial expression of Tbx2 gene during cardiac development is highly consistent and evolutionarily conserved.As a member of the T-box transcription factor family,Tbx2 plays an important role in the differentiation of outflow tract and atrioventricular canal,leading to a series of changes in the regulatory pathway by regulating the transcription levels of the downstream target genes.At present,more and more studies have indicated that aberrant expressions or regulations of Tbx2 result in cardiac malformations in different model animals.In clinical studies,microdeletions/duplications in the fragments involving TBX2 and genetic variants in the non-coding region of this gene have also been reported in human congenital heart defects.Thus,this article is to review the advances in the effect and possible mechanisms for Tbx2 gene in cardiac development,and to discuss the relationship between this gene and congenital heart defects.

TBX2 gene mutation and the clinical significance of related proteins expression in ma-lignant peripheral nerve sheath tumor / 中国肿瘤临床

Objective:To detect genomic aberrations and investigate the expression and clinical significance of TBX2,CHK2, and p53 in malignant peripheral nerve sheath tumor (MPNST) tissues. Methods:We collected 63 cases of MPNST tissue samples, which were re-moved by resection and were confirmed by pathology, from January 1991 to December 2011 in Department of Bone and Sofer Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital. Twelve fresh tumor samples with qualified DNA quality were selected from the above 63 cases of tissue samples. Genome abnormalities of 12 MPNST tissues were detected by next-generation sequencing. The protein expression levels of TBX2, CHK2, and p53 in 63 MPNST tissue samples were assessed by immunohistochemistry staining. Results:One case of TBX2 gene mutation was observed out of the 12 MPNST tissue samples. In 63 MPNST tissue samples, the protein expression rates of TBX2, CHK2, and p53 were 60.3%(38/63), 47.6%(30/63), and 30.2%(19/63), respectively. TBX2 expression was sig-nificantly correlated with AJCC (American Joint Committee on Cancer, AJCC) stage, recurrence, and metastasis (P<0.05). TBX2 expres-sion was directly correlated with that of CHK2 (r=0.254, P=0.045), and CHK2 expression was directly correlated with that of p53 (r=0.343, P=0.006). In terms of the disease-free survival and overall survival time, patients with high expression levels of TBX2, CHK2, and p53 had significantly worse prognosis than patients with low expression levels of TBX2, CHK2, and p53(all P<0.05). TBX2, CHK2, and p53 were independent prognostic factors of MPNST. Conclusion:TBX2 and its associated proteins may play important roles in MPNST development and progression. Detecting TBX2 expression may provide the theoretical basis for estimating the prognosis of patients with MPNST.

Expressions and significances of TBX2 and MDM2 protein in urothelial carcinoma of bladder / 中国医师进修杂志

Objective To evaluate the expressions of TBX2 and MDM2 protein in urothelial carcinoma of bladder.Methods The expressions of TBX2 and MDM2 protein were examined by immunohistochemistry EnvisionTM Plus method in 90 cases of urothelial carcinoma of bladder and 20 cases of normal bladder mucosa tissue.Results The positive rate of TBX2 and MDM2 protein was 0 in normal bladder mucosa tissues.The positive rate of TBX2 in urothelial carcinoma of bladder was 65.6％ (59/90).With the increased of TBX2 expression degree,the carcinoma tissue was worse cell differentiation,later clinical stage,more prone to recurrence (P ＜ 0.01).The positive rate of MDM2 in urothelial carcinoma of bladder was 31.1％(28/90).With the decreased of carcinoma tissue differentiation degree,the positive rate of MDM2 was increased (P ＜ 0.01).The positive rate of MDM2 in recurrence patients was 57.5％ (23/40),in non-recurrence patients was 10.0％ (5/50),there was statistical difference (P ＜ 0.01).The positive rate of MDM2 in pTNM stage Ta-T1 was 0,in pTNM stage T2-T3 was 73.7％ (28/38),there was statistical difference (P ＜0.01).There was positive correlation between the expression of TBX2 and MDM2 in carcinoma tissue (r =0.487,P ＜ 0.05).Conclusions The over expression of TBX2 and MDM2 protein may closely associated with aggressive biological behavior and recurrence in urothelial carcinoma of bladder.Combined analysis of TBX2 and MDM2 may provide a theoretical basis for prognostic information and treatment of patients with urothelial carcinoma of bladder.