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The development and progression of malignant tumors likely result from consecutive accumulation of genetic alterations, including dysfunctional tumor suppressor genes. However, the signaling mechanisms that underlie the development of tumors have not yet been completely elucidated. Discovery of novel tumor-related genes plays a crucial role in our understanding of the development and progression of malignant tumors. Chromosome engineering technology based on microcell-mediated chromosome transfer (MMCT) is an effective approach for identification of tumor suppressor genes. The studies have revealed at least five tumor suppression effects. The discovery of novel tumor suppressor genes provide greater understanding of the complex signaling pathways that underlie the development and progression of malignant tumors. These advances are being exploited to develop targeted drugs and new biological therapies for cancer. [ABSTRACT FROM AUTHOR]

The article discusses that Fragile X-related tremor/ataxia syndrome (FXTAS) as a neurodegenerative disease caused by CGG triplet repeat expansions in FMR1, which elicit repeat-associated non-AUG (RAN) translation and produce the toxic protein FMRpolyG. It mentions that FMRpolyG interacts with pathogenic CGG repeat-derived RNA G-quadruplexes, propagates cell to cell, and induces neuronal dysfunction.

The fields of drug discovery and regenerative medicine require large numbers of adult human primary hepatocytes. For this purpose, it is desirable to use hepatocytelike cells (HLCs) differentiated from human pluripotent stem cells (PSCs). Premature hepatoblast-like cells (HB-LCs) differentiated from PSCs provide an intermediate source and steady supply of newly mature HLCs. To develop an efficient HB-LC induction method, we constructed a red fluorescent reporter, CYP3A7R, in which DsRed is placed under the transcriptional control of CYP3A7 coding for a human fetus-type P450 enzyme. Before using this reporter in human cells, we created transgenic mice using mouse embryonic stem cells (ESCs) carrying a CYP3A7R transgene and confirmed that CYP3A7R was specifically expressed in fetal and newborn livers and reactivated in the adult liver in response to hepatic regeneration. Moreover, we optimized the induction procedure of HB-LCs from transgenic mouse ESCs using semi-quantitative fluorometric evaluation. Activation of Wnt signaling together with chromatin modulation prior to Activin A treatment greatly improved the induction efficiency of HB-LCs. BMP2 and 1.7% dimethyl sulfoxide induced selective proliferation of HB-LCs, which matured to HLCs. Therefore, CYP3A7R will provide a fluorometric evaluation system for high content screening of chemicals that induce HB-LC differentiation, hepatocyte regeneration, and hepatotoxicity when it is introduced into human PSCs. [ABSTRACT FROM AUTHOR]

The pituitary homeobox 1 (PITX1) protein is essential for developmental processes in humans. Previously, PITX1 was identified as a possible tumor suppressor gene in various types of human carcinoma. However, the association between PITX1 and human head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. Immunohistochemical analysis was performed to examine the expression levels of PITX1 in 47 cases of HNSCC, and in 4 control cases. The expression of p53 was also examined in these cases. The labeling indices (LIs) were calculated, and the correlations between clinical factors (chemosensitivity, prognosis and the degree of differentiation) and the LIs were assessed. The PITX1 LI in HNSCC was 27.4±14.5%, which was significantly lower compared with the LIs of the control samples: 76.9±6.97% (P<0.05). Additionally, the PITX1 LIs were 39.9±6.2, 26.9±16.9 and 24.2±11.8% in the complete response (CR), partial response (PR), stable disease or progressive disease (SD/PD) groups, respectively. The PITX1 LI in the CR group revealed the highest result between the all groups, and it was significantly greater compared with that in the SD/PD group (P<0.01). The p53 LIs were 24.5±19.9, 25.7±16.9 and 19.8±13.8 in the CR, PR and SD/PD groups, respectively (P>0.05). Neither the PITX1 nor the p53 LIs were a statistically significant indicator of the prognosis. PITX1 is a candidate tumor suppressor gene and a possible predictive biomarker of chemosensitivity of human HNSCC. [ABSTRACT FROM AUTHOR]

Paired-like homeodomain 1 (PITX1) genes are essential in human development. In the present study, PITX1 protein expression was evaluated in human normal oral mucosa, oral epithelial dysplasia and oral squamous cell carcinoma (OSCC), with the aim of examining the expression patterns of these critical genes during the multi-stage transformation of oral epithelial dysplasia to OSCC. PITX1 and Ki-67 expression were assessed by immunohistochemistry in 26 individuals with normal oral mucosa, 106 patients with oral epithelial dysplasia and 97 OSCC patients. The labeling indices (LIs) of PITX1 and Ki-67 were calculated and their correlation with the incidence of malignancy was evaluated. The PITX1 LI of the dysplasia specimens was significantly lower than that of the normal oral mucosa samples, but significantly higher than that of the OSCC samples. The oral epithelial dysplasia patients that exhibited low PITX1 expression showed a significantly higher incidence of malignant transformation than those exhibiting high PITX1 expression, regardless of the histological grades of their oral epithelial dysplasias. On the other hand, no correlation was observed between the Ki-67 LI and the incidence of malignancy. These results suggested that PITX1 suppression is associated with malignant transformation in the oral epithelium and that PITX1 expression may serve as a novel biomarker for predicting prognosis in oral epithelial dysplasia. [ABSTRACT FROM AUTHOR]