Cholecystokinin receptor antagonist, loxiglumide, inhibits invasiveness of human pancreatic cancer cell lines

AbstractRecently, cholecystokinin has been reported to be important in regulating the growth of pancreatic cancer. We investigated the effect of loxiglumide (LXG), a cholecytskinin receptor antagonist, on the invasiveness of two human pancreatic cancer cell lines. Cells were treated with LXG for 24 h, and examined in the invasion assay. The expression and activity of MMP-9 in supernatants from cancer cells were analyzed by Western blotting and zymogram. Interestingly, the invasiveness of cancer cells and expression of MMP-9 were decreased by LXG in a dose-dependent manner. LXG may be a useful therapeutic agent against pancreatic cancer

ARTADE2DB: Improved Statistical Inferences for Arabidopsis Gene Functions and Structure Predictions by Dynamic Structure-Based Dynamic Expression (DSDE) Analyses

Recent advances in technologies for observing high-resolution genomic activities, such as whole-genome tiling arrays and high-throughput sequencers, provide detailed information for understanding genome functions. However, the functions of 50% of known Arabidopsis thaliana genes remain unknown or are annotated only on the basis of static analyses such as protein motifs or similarities. In this paper, we describe dynamic structure-based dynamic expression (DSDE) analysis, which sequentially predicts both structural and functional features of transcripts. We show that DSDE analysis inferred gene functions 12% more precisely than static structure-based dynamic expression (SSDE) analysis or conventional co-expression analysis based on previously determined gene structures of A. thaliana. This result suggests that more precise structural information than the fixed conventional annotated structures is crucial for co-expression analysis in systems biology of transcriptional regulation and dynamics. Our DSDE method, ARabidopsis Tiling-Array-based Detection of Exons version 2 and over-representation analysis (ARTADE2-ORA), precisely predicts each gene structure by combining two statistical analyses: a probe-wise co-expression analysis of multiple transcriptome measurements and a Markov model analysis of genome sequences. ARTADE2-ORA successfully identified the true functions of about 90% of functionally annotated genes, inferred the functions of 98% of functionally unknown genes and predicted 1,489 new gene structures and functions. We developed a database ARTADE2DB that integrates not only the information predicted by ARTADE2-ORA but also annotations and other functional information, such as phenotypes and literature citations, and is expected to contribute to the study of the functional genomics of A. thaliana. URL: http://artade.org

Targeted therapy against Bcl-2-related proteins in breast cancer cells

INTRODUCTION: Bcl-2 and Bcl-xL confer resistance to apoptosis, thereby reducing the effectiveness of chemotherapy. We examined the relationship between the expression of Bcl-2 and Bcl-xL and chemosensitivity of breast cancer cells, with the aim of developing specific targeted therapy. METHODS: Four human breast cancer cell lines were examined, and the effects of antisense (AS) Bcl-2 and AS Bcl-xL phosphorothioate oligodeoxynucleotides (ODNs) on chemosensitivity were tested in vitro and in vivo. Chemosensitivity was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, and the antitumor effect was assessed in vivo by the success of xenograft transplantation into athymic mice. RESULTS: Treatment with AS Bcl-2 and Bcl-xL ODNs resulted in a sequence-specific decrease in protein expression, compared with controls. Treatment of BT-474, ZR-75-1, and MDA-MB-231 cells with AS Bcl-2 increased chemosensitivity to doxorubicin (DOX), mitomycin C (MMC), paclitaxel (TXL), and docetaxel (TXT). Transfection of the Bcl-2 gene into MDA-MB-453 cells decreased sensitivity to DOX and MMC. Treatment of MDA-MB-231, BT-474, and ZR-75-1 cells with AS Bcl-xL increased chemosensitivity to DOX, MMC and taxanes to a smaller extent than AS Bcl-2. This occurred in the setting of increased Bax and cleaved poly(ADP-ribose) polymerase, as well as decreased Bcl-2 and pAkt. AS Bcl-2 ODNs induced splenomegaly in association with increased serum IL-12, which was attenuated by methylation of the CpG motifs of AS Bcl-2; however, methylated CpG failed to negate the increased antitumor effect of AS Bcl-2. Bcl-2 and Bcl-xL, to a smaller extent, are major determinants of chemosensitivity in breast cancer cells. CONCLUSION: Targeted therapy against Bcl-2 protein with the use of AS ODNs might enhance the effects of chemotherapy in patients with breast cancer

Excision of recurrent appendix testis torsion

A 6-year-old boy developed left side scrotal pain. We diagnosed the patient as having left appendix testis torsion. We prescribed acetaminophen and the pain gradually improved. Four months after the initial episode of pain, the patient had scrotum pain again. Ultrasonography revealed a swollen appendage at the upper pole of the testis with calcification. We performed resection of the twisted appendix testis. Pathological examination revealed lymphocytic infiltration, fibrosis, edema, granulation tissue, and frequent foci of calcification. There was no necrosis. Some cases of appendix testis torsion whose initial symptoms are conservatively managed, require subsequent removal of the chronically inflamed appendage accompanied by acute inflammation for persistent or recurrent pain several months after appearance and resolution of the initial symptoms. Keywords: Acute scrotum, Torsion of appendix testis, Recurrence symptom