Background-The functional changes associated with cellular senescence may be involved in human aging and age-related vascular disorders. We have shown the important role of telomere and telomerase in vascular cell senescence in vitro. Progressive telomere shortening in vivo has been observed in the regions susceptible to atherosclerosis, implying contributions to atherogenesis. However, whether senescent vascular cells are present in the vasculature and contribute to the pathogenesis of atherosclerosis remains unclear. Methods and Results-Senescence-associated ␤-galactosidase (␤-gal) activity was examined in the coronary arteries and the internal mammary arteries retrieved from autopsied individuals who had had ischemic heart diseases. Strong ␤-gal stainings were observed in atherosclerotic lesions of the coronary arteries but not in the internal mammary arteries. Key Words: aging Ⅲ atherosclerosis Ⅲ endothelium C ellular senescence is a limited ability of primary human cells to divide when cultured in vitro. This cessation of cell division is accompanied by a specific set of changes in cell function, morphology, and gene expression. These changes in cell phenotype may contribute to age-associated diseases, including atherosclerosis. However, cellular senescence has largely been investigated in vitro, and the presence of senescent vascular cells in vivo has not been clarified.Recently, accumulating evidence has suggested a critical role of telomere and telomerase in cellular senescence in vitro. 1 We have demonstrated previously that the introduction of telomerase catalytic component (TERT) into human vascular smooth muscle cells extends cell life span and preserves a younger phenotype, suggesting that telomere stabilization is important for long-term cell viability of vascular cells. 2 Progressive telomere shortening in human arteries has been observed in the regions susceptible to atherosclerosis. 3 Moreover, telomere length has been reported to inversely correlate with pulse pressure and atherosclerotic grade in human. 4,5 Although these observations imply that telomere shortening in vivo may contribute to the pathogenesis of age-associated vascular disorders, it remains unclear whether loss of telomere function induces vascular dysfunction associated with aging.In the present study, we demonstrate the presence of vascular endothelial cells with senescence-associated phenotypes in the atherosclerotic regions of human coronary arteries. We also show that loss of telomere function induces endothelial dysfunctions that are observed in aged arteries, whereas inhibition of telomere shortening suppresses these alterations with senescence. Methods Tissue SpecimensHuman coronary arteries and internal mammary arteries were obtained from 4 autopsied individuals who had ischemic heart diseases. The autopsy tissues were obtained within 12 hours after death and were subjected to ␤-galactosidase (␤-gal) staining. HistologySenescence-associated ␤-gal activity was examined in the tissues as described previously. 6 Briefly, t...

We regard sialolipoma as a distinct variant of salivary gland lipoma that can occur in both the major and minor salivary glands. Superficial parotidectomy, or surgical resection in the case of palatal tumours, is an appropriate treatment for this benign tumour.

Background:Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed.Methods:Next-generation sequencing revealed 945–1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC). Genome-wide gene expression studies and in silico analyses were carried out to predict miRNA regulation and investigate the functional significance and clinical utility of the novel oncogenic pathways regulated by these miRNAs in prostate cancer (PCa).Results:Based on the novel miRNA expression signature of CRPC, miR-145-5p and miR-145-3p were downregulated in CRPC. By focusing on miR-145-3p, which is a passenger strand and has not been well studied in previous reports, we showed that miR-145-3p targeted 4 key molecules, i.e., MELK, NCAPG, BUB1, and CDK1, in CPRC. These 4 genes significantly predicted survival in patients with PCa.Conclusions:Small RNA sequencing for lethal CRPC and in silico analyses provided novel therapeutic targets for CRPC.

Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade "dedifferentiated" carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34-70 y). The mean size of the tumors was 3.5 cm (range, 1.7-6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6-69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immunoreactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of 1 case, which was positive for p53 immunostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma.