Gene Expression Signature of DMBA-Induced Hamster Buccal Pouch Carcinomas: Modulation by Chlorophyllin and Ellagic Acid

Chlorophyllin (CHL), a water-soluble, semi-synthetic derivative of chlorophyll and ellagic acid (EA), a naturally occurring polyphenolic compound in berries, grapes, and nuts have been reported to exert anticancer effects in various human cancer cell lines and in animal tumour models. The present study was undertaken to examine the mechanism underlying chemoprevention and changes in gene expression pattern induced by dietary supplementation of chlorophyllin and ellagic acid in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model by whole genome profiling using pangenomic microarrays. In hamsters painted with DMBA, the expression of 1,700 genes was found to be altered significantly relative to control. Dietary supplementation of chlorophyllin and ellagic acid modulated the expression profiles of 104 and 37 genes respectively. Microarray analysis also revealed changes in the expression of TGFβ receptors, NF-κB, cyclin D1, and matrix metalloproteinases (MMPs) that may play a crucial role in the transformation of the normal buccal pouch to a malignant phenotype. This gene expression signature was altered on treatment with chlorophyllin and ellagic acid. Our study has also revealed patterns of gene expression signature specific for chlorophyllin and ellagic acid exposure. Thus dietary chlorophyllin and ellagic acid that can reverse gene expression signature associated with carcinogenesis are novel candidates for cancer prevention and therapy

Experimental investigation on microstructural and mechanical properties of quenched AISI 4145 sinter forged steel

149-154In the present investigation, microstructure and mechanical properties of sinter - forged AISI 4145 steel have been examined. Homogeneous powder blend of steel corresponding to AISI 4145 composition has been taken to prepare the compacts of 30 mm diameter with 1.0 aspect ratio on hydraulic press using suitable die assembly. Protective coated green compact preforms have been sintered at 1150° C ± 10° C for a period of 90 min. Subsequently, the sintered preforms have been hot upset forged to square cross-sectional bars (~13 mm × ~13 mm) with the length of 110 ± 5 mm. Further, the bars have been quenched in oil with and without homogenization. Mechanical properties such as tensile strength, yield strength, percentage elongation, and impact strength have been analysed. Optical microscopy (OM), scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies have been used to characterize the metallurgical features of the steel on different oil quenched condition. Microstructure reveals the ferrite, pearlite and non-equilibrium marten site structures in the sinter-forged low alloy steel. Sinter forged steel exhibits enhanced strength and hardness in homogenized oil quenched condition

Gene expression profiling identifies a unique androgen-mediated inflammatory/immune signature and a PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10)-mediated apoptotic response specific to the rat ventral prostate

Understanding androgen regulation of gene expression is critical for deciphering mechanisms responsible for the transition from androgen-responsive (AR) to androgen-independent (AI) prostate cancer (PCa). To identify genes differentially regulated by androgens in eachprostate lobe, the rat castration model was used. Microarray analysis was performed to compare dorsolateral (DLP) and ventral prostate (VP)samples from sham-castrated, castrated, and testosterone-replenished castrated rats. Our data demonstrate that, after castration, the VP and the DLP differed in the number of genes with altered expression (1496in VP vs. 256 in DLP) and the nature of pathways modulated. Gene signatures related to apoptosis and immune response specific to the ventral prostate were identified. Microarray and RT-PCR analysesdemonstrated the androgen repression of IGF binding protein-3 and -5,CCAAT-enhancer binding protein-\delta, and phosphatase and tensin homolog deleted on chromosome 10 ( PTEN) genes, previously implicated in apoptosis. We show that PTEN protein was increased only in the luminal epithelial cells of the VP, suggesting that it may be a key mediator of VP apoptosis in the absence of androgens. The castration-induced immune/inflammatory gene cluster observed specifically in the VP included IL-15 and IL-18. Immunostaining of the VP, but not the DLP, showed an influx of T cells, macrophages, and mast cells, suggesting that these cells may be the source of the immune signature genes. Interestingly, IL-18 was localized mainly to the basal epithelial cells and the infiltrating macrophages in the regressing VP,whereas IL-15 was induced in the luminal epithelium. The VP castration model exhibits immune cell infiltration and loss of PTEN that is often observed in progressive PCa, thereby making this model useful for further delineation of androgen-regulated gene expression with relevance to PCa