Expression and allele frequencies of Thymic stromal lymphopoietin are a key factor of breast cancer risk.

BACKGROUND: Thymic stromal Lymphopoeitin (TSLP) is a key cytokine involved in inflammation and cancer progression. TSLP gene polymorphisms have been associated with increased susceptibility to cancer progression in different organs. We performed a control case study to examine the correlation of expression and polymorphisms of three nucleotides in TSLP with breast cancer (BC) risk in Saudi Arabian females. MATERIALS AND METHODS: The study was conducted on 116 healthy control subjects and 127 female patients with BC for the purpose of genotyping. Ten matching tissues provided data on immunohistochemistry to evaluate TSLP expression. Three SNPs (rs10043985, rs2289276, and rs3806933) were genotyped with TaqMan allelic discrimination assay. The patients' ages and estrogen receptor statuses were used to investigate the potential correlations between the different variations of TSLP genotypes and BC risk. RESULTS: BC tissues expressed positive immuno-staining for TSLP at a high rate compared to normal matching breast tissues. Malignant breast tumors exhibited higher TSLP expression than benign breast tumors. We also found that the rs3806933 (T) allele frequency decreased the risk of developing BC in the study population (OR = 0.356, p = 0.00027) significantly (0.356 times). Interestingly, statistical analysis revealed that the genotype mutant (AC) and the allele mutant (C) of rs10043985 within TSLP were significantly correlated with an increased BC risk (odds ratio [OR] = 4.762, confidence interval [CI] = 1.000-22.666, p = 0.03244; OR = 4.762, CI = 1.000-22.666, p = 0.03244; and OR = 4.575, CI = 0.975-21.464, p = 0.03516, respectively). In addition, the AC and AC + CC genotypes of TSLP rs10043985 were confirmed to be associated with an increased risk of BC risk in women aged above 48 years, compared with the AA genotype (AC and AC + CC vs. AA: OR = 9.468, CI = 0.493-181.768, p = 0.04537). CONCLUSION: The results reveal significant correlation between SNPs in TSLP and BC progression in Saudi Arabian female patients.

Samsum Ant Venom Exerts Anticancer Activity Through Immunomodulation In Vitro and In Vivo.

Samsum ant venom (SAV) is a rich repertoire of natural compounds with tremendous pharmacological properties. The present work explores its antineoplastic activity in different cell lines followed by its confirmation in vivo. The cell lines, HepG2, MCF-7, and LoVo showed the differential dose-dependent antineoplastic effect with an increased level of significant cytokines, including Interleukin (IL)-1ß, IL-6, and IL-8 and transcription factor, Nuclear factor-kappa B (NF-κB). However, the venom was more effective on HepG2 and MCF-7 cells than LoVo cells. Furthermore, the extract was administered to four groups (n = 8) of rats. Group I was taken as a control without any treatment, whereas group II received CCl4 (1 mL/kg) for induction of mild hepatoma. Group III was given 100 µg/kg of SAV twice a week for 1 month. Group IV was pretreated with the CCl4 (like group II) followed by dosing with SAV (100 µg/kg) for 2 months as per the authors' prestandardized dosing schedule. Intriguingly, the rats of group IV demonstrated significant decrease in key cytokines, IL-1ß and IL-6, as well as the transcription factors, including Tumor Necrosis Factor-alpha (TNF-α), NF-κB, and Inhibitor-kappa B (I-κB) as compared with group II. Furthermore, increase in IL-10 and First apoptosis signal (FAS) in the same group confirmed that SAV induces apoptosis at the given dose through immunomodulation leading to enhanced tumor killing in vivo. Hence, SAV has an excellent antineoplastic activity that can be directly used to treat certain types of cancer. Moreover, study of its ingredients can pave ways to design novel anticancer drugs. However, further in-depth investigation is required before its clinical trials.

Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.

The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human ß-defensins (hBDs) are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4) and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR) and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs) and the potential development of colon cancer.

Molecular cloning and characterization of cDNA encoding a putative stress-induced heat-shock protein from Camelus dromedarius.

Heat shock proteins are ubiquitous, induced under a number of environmental and metabolic stresses, with highly conserved DNA sequences among mammalian species. Camelus dromedaries (the Arabian camel) domesticated under semi-desert environments, is well adapted to tolerate and survive against severe drought and high temperatures for extended periods. This is the first report of molecular cloning and characterization of full length cDNA of encoding a putative stress-induced heat shock HSPA6 protein (also called HSP70B') from Arabian camel. A full-length cDNA (2417 bp) was obtained by rapid amplification of cDNA ends (RACE) and cloned in pET-b expression vector. The sequence analysis of HSPA6 gene showed 1932 bp-long open reading frame encoding 643 amino acids. The complete cDNA sequence of the Arabian camel HSPA6 gene was submitted to NCBI GeneBank (accession number HQ214118.1). The BLAST analysis indicated that C. dromedaries HSPA6 gene nucleotides shared high similarity (77-91%) with heat shock gene nucleotide of other mammals. The deduced 643 amino acid sequences (accession number ADO12067.1) showed that the predicted protein has an estimated molecular weight of 70.5 kDa with a predicted isoelectric point (pI) of 6.0. The comparative analyses of camel HSPA6 protein sequences with other mammalian heat shock proteins (HSPs) showed high identity (80-94%). Predicted camel HSPA6 protein structure using Protein 3D structural analysis high similarities with human and mouse HSPs. Taken together, this study indicates that the cDNA sequences of HSPA6 gene and its amino acid and protein structure from the Arabian camel are highly conserved and have similarities with other mammalian species.