Molecular Therapeutic Targets for Glioma Angiogenesis

Due to the prominent angiogenesis that occurs in malignant glioma, antiangiogenic therapy has been attempted. There have been several molecular targets that are specific to malignant gliomas, as well as more broadly in systemic cancers. In this review, I will focus on some topics related to molecular therapeutic targets for glioma angiogenesis. First, important angiogenic factors that could be considered molecular targets are VEGF, VEGF-induced proteins on endothelial cells, tissue factor, osteopontin, αvβ3 integrin, and thymidine phosphorylase as well as endogenous inhibitors, soluble Flt1, and thrombospondin 1. Second, hypoxic areas are also decreased by metronomic CPT11 treatment as well as temozolomide. Third, glioma-derived endothelial cells that are genetically and functionally distinct from normal endothelial cells should be targeted, for example, with SDF-1 and CXCR7 chemokine. Fourth, endothelial progenitor cells (EPCs) likely contribute towards glioma angiogenesis in the brain and could be useful as a drug delivery tool. Finally, blockade of delta-like 4 (Dll4) results in a nonfunctioning vasculature and could be another important target distinct from VEGF

グリオブラストーマ由来血管の発生機序とその性質がもたらす悪性度への影響

科学研究費助成事業 研究成果報告書：基盤研究(C)2015-2017課題番号 : 15K0682

A Case of Cystic Basal Cell Carcinoma Which Shows a Homogenous Blue/Black Area under Dermatoscopy

Basal cell carcinoma (BCC) is the most common skin tumor and contains several different histopathological types. Here, we report a case of cystic basal cell carcinoma, which is relatively rare and might be clinically misdiagnosed. A dermatoscopic examination of the case revealed a homogenous blue/black area usually not seen in BCC. We reviewed 102 BCC cases resected and diagnosed at Sapporo Medical University Hospital between April 2005 and March 2010. Among them, only three were the cystic type

Modulation of Growth and Transformation of Murine MC3T3-E1 Cell Line by Murine Wild-type and Mutant p53 Genes

We studied the effects of murine wild-type and mutant p53 genes (p53-wt and p53val135) on the growth and transformation of murine osteoblastoid cell line MC3T3-El. The mutant p53val135 enhanced focus formation of MC3T3-E1 cells by the activated H-ras plus LTR-myc gene and H-ras plus adenovirus 12 E1A gene more than four fold each, while p53-wt suppressed them 0.4 and 0.3 fold, respectively. The plating efficiency of hygromycin-resistant MC3T3-E1 cells after transfection of pSV2hygro were also increased by more than three fold with the cotransfection of p53val135 and the efficiency was also decreased 0.2 fold by cotransfection of p53-wt. These indicate that p53val135 enhances and p53-wt suppresses not only oncogene focus formation but also the cellular growth of the murine MC3T3-E1 cell line. Southern blot hybridization detected the tran-sfected p53-wt sequence only in three out of ten MC3T3-E1 cell lines established from foci induced by p53-wt and oncogenes, and failed to detect the p53-wt DNA in hygromycin-resistant MC3T3-E1 cell lines transfected with pSV2hygro and p53-wt. These suggest that MC3T3-E1 cells containing p53-wt are at a dis-advantage to form transformed foci or colonies, and suggests that MC3T3-E1 provides a good in vitro system to test the biological activity of murine wild-type and mutant p53 genes

SIRT1 negatively regulates the expression of Prl2C3,a senescence-associated protein

SIRT1 is a mammalian homologue of yeast longevity protein Sir2. SIRT1 deacetylates transcription factors, cofactors, and histones in an NAD+-dependent manner, and promotes cell survival, anti-oxidative function, and DNA repair. Although some studies have indicated that SIRT1 is involved in longevity, the function of SIRT1 for preventing aging and senescence is still unclear. In mouse embryonic fibroblasts (MEFs), we found that SIRT1 expression decreased by aging and IRT1 reciprocally regulated the expression level of Prl2C3, one of the prolactin-like peptides. In young MEFs, purified Prl2C3 inhibited the growth and increased the number of senescence-associated β galactosidase-positive cells with enlarged and flattened shapes. Moreover, immunostaining of human skin sections showed the expression of Prl2C3 in the basal cells of the epidermis. These results indicate that SIRT1 negatively regulates a senescence-associated protein rl2C3

Surface-spreading technique of meiotic cells and immunodetection of synaptonemal complex proteins in teleostean fishes

Background: Different moderrn methodologies are presently available to analyze meiotic chromosomes. These methods permit investigation of the behavior of chromosomes in the normal complement and of sex and B chromosomes, two special types of chromosomes that are associated with the A complement and are present in many organisms, including fishes. However, meiotic studies are still scarce in fishes, considering the wide number of species in this group.. Here, we describe a new protocol for the visualization of the synaptonemal complex in spermatocytes and oocytes of fishes and to the sequential use of the technique with other procedures and techniques such as immunodetection of the synaptonemal complex protein with a specific antibody and co-detection of DNA sequences by FISH.Results: The meiotic surface-spreading protocol used in the present proposal worked well in representative species of four fish orders and was useful in obtaining good results even in small specimens. Fish-specific antibodies and commercial products worked similarly well to detect synaptonemal complex (SC) proteins. The sequential application of fluorescence in situ hybridization using specific probes showed clear signals associated with the SC structures identified by immunostaining.Conclusion: Here, we provide a useful and applicable immunofluorescent protocol for the visualization of synaptonemal complex proteins in the meiotic cells of fishes in surface-spreading preparations. Furthermore, this technique allows for the sequential application of other cytogenetic procedures.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES