Three discrete areas within the chromosomal 8p21.3–23 region are associated with the development of breast carcinoma of Indian patients

Deletion in the 22.9 -Mb chromosomal (chr.) 8p21.3-23 region has been shown to be necessary for the development of breast carcinoma (CaBr). In this study, we have attempted to detect the minimal deleted region(s) in the chr.8p21.3-23 region in 62 primary breast lesions having 56 CaBr tumors and six other breast lesions of Indian patients using 15 microsatellite markers. The loss of heterozygosity (LOH) was observed for at least one marker in 96.4% (54/56) of the CaBr samples. Three discrete minimal deleted regions with high frequencies of LOH (39-65%) were identified in the chromosomal 8p23.1-23.2 (D1), 8p23.1 (D2) and 8p 21.3-22 (D3) regions within 2.03, 0.41, 2.47 Mb, respectively. No significant correlation was observed with the high deleted regions and the different clinicopathological parameters. Interestingly, 51.8% (29/56) CaBr samples showed either loss of chr.8p or interstitial deletions in this arm, indicating the importance of chr.8p in the development of CaBr. The pattern of allelic loss in the bilateral lesions had indicated that the lesions were clonal in origin and probably the deletion in the D3 region was the early event among the D1-D3 regions. Thus, our data have indicated that the D1-D3 regions could harbor candidate tumor suppressor gene(s) (TSGs) associated with the development of CaBr

Frequent Deletion and Methylation in SH3GL2 and CDKN2A Loci are Associated with Early- and Late-onset Breast Carcinoma

This study attempts to understand the association of candidate tumour suppressor genes SH3GL2, CDKN2A (p16–p14) and CDKN2B (p15) in development of earlyonset (group A) and late-onset (group B) breast carcinoma (BC). Deletion, methylation, and mutation of the candidate tumour suppressor genes (TSGs) were analysed in 47 group A and 59 group B samples. Immunohistochemical analysis was used to identify the expression status of SH3GL2 and p16. Clinicopathological correlation of the alterations was analysed by the chi-square and log-rank tests. Higher frequency of overall alterations (46–62%) in SH3GL2 and p16-p14 than p15 (22–26%) indicated their importance in BC. Deletion frequencies were in the following order: group A: p14 (43%) > p16 (42%) > SH3GL2 (38%) > p15 (33%) and group B: p14 (36%) > p16 (33%) > SH3GL2 (31%) > p15 (14%) while, methylation frequencies were: group A: SH3GL2 (34%) > p16 (28%) > p14 (26%) > p15 (15%) and group B: SH3GL2 (36%) > p16 (31%) > p14 (29%) > p15 (15%). Infrequent mutation was observed only in CDKN2A common exon-2. Immunohistochemical analysis showed significant association between expression of SH3GL2 and p16 with their deletion (P = 0.01 and 0.02, respectively) and methylation status (P = 0.007 and 0.01, respectively). In group A, overall alterations of SH3GL2 showed significant association with CDKN2A locus with significant prognostic implications, whereas CDKN2A and CDKN2B loci were associated in both groups.The molecular mechanisms involving CDKN2A inactivation seem to follow similar pathway in the pathogenesis of both age groups of BC while significant association of SH3GL2 with CDKN2A might play a synergistic role in the development of group A

Modifying of Cotton Fabric Surface with Nano-ZnO Multilayer Films by Layer-by-Layer Deposition Method

<p>Abstract</p> <p>ZnO nanoparticle&#8211;based multilayer nanocomposite films were fabricated on cationized woven cotton fabrics via layer-by-layer molecular self-assembly technique. For cationic surface charge, cotton fabrics were pretreated with 2,3-epoxypropyltrimethylammonium chloride (EP3MAC) by pad-batch method. XPS and SEM were used to examine the deposited nano-ZnO multilayer films on the cotton fabrics. The nano-ZnO films deposited on cotton fabrics exhibited excellent antimicrobial activity against <it>Staphylococcus aureus</it> bacteria. The results also showed that the coated fabrics with nano-ZnO multilayer films enhanced the protection of cotton fabrics from UV radiation. Physical tests (tensile strength of weft and warp yarns, air permeability and whiteness values) were performed on the fabrics before and after the treatment with ZnO nanoparticles to evaluate the effect of layer-by-layer (LbL) process on cotton fabrics properties.</p

Deletions in Chromosome 4 Differentially Associated With the Development of Cervical Cancer: Evidence of Slit2 as a Candidate Tumor Suppressor Gene

The aim of this study was to locate the candidate tumor suppressor genes (TSGs) loci in the chromosomal 4p15-16, 4q22-23 and 4q34-35 regions associated with the development of uterine cervical carcinoma (CA-CX). Deletion mapping of the regions by microsatellite markers identified six discrete areas with high frequency of deletions, viz. 4p16.2 (D1: 40%), 4p15.31 (D2: 35–38%), 4p15.2 (D3: 37–40%), 4q22.2 (D4: 34%), 4q34.2-34.3 (D5: 37–59%) and 4q35.1 (D6: 40–50%). Significant correlation was noted among the deleted regions D1, D2 and D3. The deletions in D1, D2, D5 and D6 regions are suggested to be associated with the cervical intraepithelial neoplasia (CIN), and deletions in the D2, D3, D5 and D6 regions seems to be associated with progression of CA-CX. The deletions in the D2 and D6 regions showed significant prognostic implications (P = 0.001; 0.02). The expression of the candidate TSG SLIT2 mapped to D2 region gradually reduced from normal cervix uteri fi CIN fi CA-CX. SLIT2 promoter hypermethylation was seen in 28% CIN samples and significantly increased with tumor progression (P = 0.04). Significant correlation was seen between SLIT2 deletion and its promoter methylation (P = 0.001), indicating that both these phenomena could occur simultaneously to inactivate this gene. Immunohistochemical analysis showed reduced expression of SLIT2 in cervical lesions and CA-CX cell lines. Although no mutation was detected in the SLIT2 promoter region (–432 to + 55 bp), CC and AA haplotypes were seen in –227 and –195 positions, respectively. Thus, it indicates that inactivation of SLIT2- ROBO1 signaling pathway may have an important role in CA-CX development

Extracellular vesicles derived from T regulatory cells suppress T cell proliferation and prolong allograft survival

We have previously shown that rat allogeneic DC, made immature by adenoviral gene transfer of the dominant negative form of IKK2, gave rise in-vitro to a unique population of CD4+CD25- regulatory T cells (dnIKK2-Treg). These cells inhibited Tcell response in-vitro, without needing cell-to-cell contact, and induced kidney allograft survival prolongation in-vivo. Deep insight into the mechanisms behind dnIKK2-Treg-induced suppression of Tcell proliferation remained elusive. Here we document that dnIKK2-Treg release extracellular vesicles (EV) riched in exosomes, fully accounting for the cell-contact independent immunosuppressive activity of parent cells. DnIKK2-Treg-EV contain a unique molecular cargo of specific miRNAs and iNOS, which, once delivered into target cells, blocked cell cycle progression and induced apoptosis. DnIKK2-Treg-EV-exposed T cells were in turn converted into regulatory cells. Notably, when administered in-vivo, dnIKK2-Treg-EV prolonged kidney allograft survival. DnIKK2-Treg-derived EV could be a tool for manipulating the immune system and for discovering novel potential immunosuppressive molecules in the context of allotransplantation