SP1 mediates the link between methylation of the tumour suppressor miR‐149 and outcome in colorectal cancer

Although recent studies indicate that DNA methylation contributes to the down‐regulation of microRNAs (miRNAs) in colorectal cancer (CRC), this field remains largely unexplored. To identify methylation‐silenced miRNAs and clarify their role in CRC, we performed a microarray analysis and screened for miRNAs that were induced in CRC cells by 5‐aza‐2′‐deoxycytidine treatment or by the knockdown of DNA methyltransferases. The DNA methylation status of the candidate miRNA was analysed by bisulphite sequencing PCR and methylation‐specific PCR. We found that miRNA‐149 (miR‐149) was epigenetically silenced in CRC and down‐regulation of miR‐149 was associated with hypermethylation of the neighbouring CpG island (CGI). Quantitative RT‐PCR analysis demonstrated that the miR‐149 level was markedly reduced in 51.6% of the CRC tissues compared with matched non‐cancerous tissues. In addition, low expression of miR‐149 was associated with a greater depth of invasion ($\it{p} = 0.012$ ), lower 5‐year survival rate ($\it{p} = 0.025$ ), and was found to be an independent prognostic factor for overall survival ($\it{p} = 0.016$ ) in a multivariate analysis. Moreover, transfection of miR‐149 inhibited cell growth and invasion of CRC cells in vitro. We also identified mRNA for Specificity Protein 1 (SP1, Sp1), a potential oncogenic protein, as a target of miR‐149. Our data suggest that, as a methylation‐sensitive miRNA, miR‐149 may play an important role as a tumour suppressor in CRC, which has prognostic and therapeutic implications. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The miRNA‐149‐5p/MyD88 axis is responsible for ursolic acid‐mediated attenuation of the stemness and chemoresistance of non‐small cell lung cancer cells

Although the inhibitory roles of ursolic acid (UA) have been established in various tumors, its effects on the stemness of non‐small cell lung cancer (NSCLC) cells are still unclear. Here, we constructed NSCLC cells with paclitaxel resistance (A549‐PR) and showed that A549‐PR exhibited a remarkably stronger stemness than the parental A549 cells, which is evident by the increase of spheroid formation capacity, stemness marker expression, and ALDH1 activity. Additionally, UA significantly reduced the stemness and paclitaxel resistance of A549‐PR cells. Mechanistic investigations revealed that UA inhibited the miR‐149‐5p/MyD88 signaling, which is responsible for UA‐mediated effects on the stemness of A549‐PR cells. Notably, miR‐149‐5p/MyD88 axis promoted the stemness of A549 cells, while inhibition of this axis attenuated the stemness of A549‐PR cells. Therefore, these results suggest that UA could attenuate the stemness and chemoresistance of NSCLC cells through targeting miR‐149‐5p/MyD88 axis.     

Biliary spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) in dogs

The spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) on the biliary tract was investigated in anesthetized dogs. Intravenous administration of AA-149 at 2 mg/kg and higher doses produced a dose-dependent reduction in passage resistance through the choledochoduodenal junction and in gallbladder pressure, and a dose-dependent increase in bile flow. AA-149, like cholecystokinin, decreased biliary ductal pressure in spite of increasing the bile flow in dogs with ligation of the cystic duct of the gallbladder, whereas taurocholate increased the pressure as well as the bile flow. Moreover, the spasmic response of the choledochoduodenal junction to morphine was depressed strongly by AA-149, BUT NOT CONSISTENTLY BY ATROPINE. The effects of AA-149 were not influenced by pretreatment with atropine, phentolamine or propranolol. These findings strongly suggest that AA-149 relaxed the biliary tract and depressed the morphine-induced spasm by a mechanism different from those of anticholinergic and sympathomimetic agents.     

Cholelithiasis and ileal pathology in childhood.

Primary cholelithiasis is rare in childhood. A particular etiology has appeared over the last few years in connection with unusual physiological situations. Three cases of cholelithiasis after ileal atresia or resection are presented in children of 1, 1, and 7 yr. Another case is presented after abdominal irradiation for Wilms' tumor and ileal resection in a child of 7. The pathogenesis is discussed, raising the question of the interruption of the enterohepatic circulation of bile salts.     

Intentional replantation: a case report of a mandibular first molar with a three-year followup

A case of intentional replantation of a mandibular first molar that has remained clinically asymptomatic and appears radiographically successful for over three years has been reported. This case serves as a reminder that replantation can provide additional years of function for teeth that otherwise would be consid- ered hopeless.     

Membranous glomerulonephritis and hepatitis B surface antigen in children.

Of 33 children with membranous nephropathy screened for HBs Ag, 14 were found to be HBs Ag carriers, whereas HBs Ag was detected in 3 of 170 and 4 of 100 children with glomerular and nonglomerular kidney diseases, respectively. HBs Ag was often associated with acute hepatitis at onset (five patients) or with elevated transminases values. This high incidence and the prevalence of an unusual subtype (ayw2) suggest a relationship between HBs Ag and the glomerular lesions. Using immunofluorescence, however, HBs Ag could not be detected within the deposits, so that the nature of the relationship cannot be considered as established. The clinical outcome (50% remission), the plasma complement component disturbances, and findings by immunofluorescence did not differ from those observed in children with MGN without detectable HBs Ag.     

Everolimus-Induced Systemic Serositis After Simultaneous Liver and Kidney Transplantation: A Case Report

Although everolimus, a mammalian target of rapamycin inhibitor, has been used as a potent immunosuppressive agent in organ transplantation, data regarding its adverse effect profile compared with that of sirolimus in clinical circumstances are limited. A 50-year-old man who underwent simultaneous liver and kidney transplantation 14 months previously was admitted with large pleural effusion, pericardial effusion, and ascites. Laboratory findings and cultures for possible infectious causes were all negative. Pericardial window surgery with drainage of the pericardial fluid was performed on day 3. Pleural and pericardial biopsy revealed non-specific inflammation without evidence of malignant cells. Everolimus was discontinued and replaced by mycophenolate mofetil on day 4. Significant clinical improvement was observed after discontinuation of everolimus, and follow-up echocardiography and chest radiography showed no recurrence of the pericardial or pleural effusion after discharge.     

Cytogenetic forms of retinoblastoma: their incidence in a survey of 66 patients

Sixty-six retinoblastoma patients were investigated using high resolution banding techniques, sister chromatid exchange (SCE) studies, and esterase-D phenotype determination and dosage. Seven patients (in six families) were found to be carriers of a rearrangement of band 13q14 due to de novo deletions, apparently balanced de novo translocations, or parental insertions. The possible role of submicroscopic parental insertions is suggested to explain transmission of nonchromosomal forms through unaffected carriers.