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

Effect of Retinoic Acid on the Growth and the Expression of the Human Papillomavirus 16 E6 and E7 Genes of the Cervical Carcinoma Cell Lines

Human papillomavirus type 16 (HPV16) is involved in the development of cervical carcinoma and its viral gene products E6 and E7 are believed to be essential for the carcinogenic process. We analyzed the effect of retinoic acid (RA) on the growth and/or HPV16 E6 and E7 gene expression in the HPV16-containing cervical carcinoma cell lines SiHa, CaSki and QG-U and the HPV-free cell lines C33A and EBC-1. RA (10-6 M) suppressed the growth of SiHa cells by more than 90% and of QG-U cells by about 40% ; however, the growth of CaSki, C33A and EBC-1 cells was not affected by RA. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was applied for investigation of the relationship between RA and the level of HPV16 E6/E7 mRNA. As a result, the E6/E7 mRNA level in SiHa and QG-U was reduced by RA by about 60% and 75%, respectively, while RA had no obvious effect on the E6 and E7 gene expression in CaSki cells. The chloramphenicol acetyltransfer-ase (CAT) assay showed that transcription driven by HPV16 non-coding region (NCR) was suppressed by RA by about 75%. These results suggest that at least a part of the growth suppression of SiHa and QG-U by RA is mediated by sup-pression of E6 and E7 expression