Search

Triple negative breast cancer (TNBC) is an aggressive phenotype of breast cancer with reduced survival and poor prognosis. Increased VEGF-A, IGF-I, IGF-IR and TGF-β1 expressions were detected in breast cancer. However, little is known about their prognostic and predictive roles in TNBC.We assessed the possible prognostic and predictive values of VEGF-A, IGF-I/IGF-IR and TGF-β1 in TNBC cases by measuring their protein and mRNA expression in TNBC and non-TNBC cases.VEGF-A, IGF-I, IGF-IR and TGF-β1 RNA and their corresponding proteins were assessed in 43 TNBCs, 53 non-TNBCs and 30 normal breast tissues (NBT) by real time PCR (qPCR) and immunohistochemistry (IHC); respectively. Results were related to clinico-pathological factors, response to treatment and survival rates.Increased mRNA expression of VEGF-A, IGF-I, and IGF-IR was significantly higher in TNBC (65.1%, 65.1%, and 72.1%) than non-TNBC (28.1%, 33.96% and 28.3%) and NBT (0.00%) (P0.001). Similarly, TNBC patients were significantly associated with high expression of VEGF-A, IGF-I, and IGF-IR proteins (67.44%, 62.79% and 83.72%) than non-TNBC (20.75%, 35.86% and 20.75%) and NBT (0.00%) (P0.001). Protein and RNA expression levels of all studied markers showed high concordance in all investigated patients (correlation coefficient exceeding 0.5 and 0.4, respectively). In the TNBC group, metastasis and poor response to treatment were significantly associated with VEGF-A (P0.001, P=0.007, respectively), IGF-I (P0.001, P0.001, respectively), IGF-IR (P=0.001, P=0.015, respectively) and TGF-β1 (P0.001, P=0.007, respectively) protein levels. Multivariate logistic regression showed that IGF-I was the only independent prognostic factor for reduced OS (P=0.034) and DFS (P=0.026) in the TNBC patients.VEGF-A, IGF-I and IGF-IR play an important role in the development and progression of TNBC compared to non-TNBC. Therefore, they could be used as prognostic and predictive biomarkers as well as candidates for targeted therapy. However, only IGF-I can predict survival in those patients.

Hyaluronidase (HAase) was reported as a urinary marker of bladder cancer. In this study, a simple colorimetric gold nanoparticle (AuNP) assay was developed for rapid and sensitive detection of urinary HAase activity. Charge interaction between polyanionic hyaluronic acid (HA) and cationic AuNPs stabilized with cetyl trimethyl ammonium bromide (CTAB) led to formation of gold aggregates and a red to blue color shift. HAase digests HA into small fragments preventing the aggregation of cationic AuNPs. The nonspecific aggregation of AuNPs in urine samples was overcome by pre-treatment of samples with the polycationic chitosan that was able to agglomerate all negatively charged interfering moieties before performing the assay. The developed AuNP assay was compared with zymography for qualitative detection of urinary HAase activity in 40 bladder carcinoma patients, 11 benign bladder lesions patients and 15 normal individuals, the assay sensitivity was 82.5% vs. 65% for zymography, while the specificity for both assays was 96.1%. The absorption ratio, A530/A620 of the reacted AuNP solution was used to quantify the HAase activity. The best cut off value was 93.5 μU/ng protein, at which the sensitivity was 90% and the specificity was 80.8%.The developed colorimetric AuNP HAase assay is simple, inexpensive, and can aid noninvasive diagnosis of bladder cancer.

Deltamethrin is a synthetic pyrethroid insecticide used extensively in pest control. Aim of the current study was to investigate the ability of deltamethrin-based commercial formulation to induce genotoxicity and testicular injury in rats in comparison to the use of the biopesticide; Bacillus thuringiensis. Rats were divided into three groups: Group I (DEL) received deltamethrin, 5 mg/kgb.w./day orally, in corn oil. Group II (Biopesticide, B. thuringiensis) received oral suspension of the biopesticide at daily dose of 8400 mg/kgb.w./day. Group III (Control) received appropriate volume of corn oil. After 4 weeks, deltamethrin-treated rats showed decreased serum testosterone, luteinizing and follicle-stimulating hormone levels. Testicular total oxidant capacity (TOC), poly (ADP-ribose) polymerase (PARP), lactate dehydrogenase (LDH) and DNA damage were significantly increased. Significant increase in bone marrow chromosomal aberrations, induced by deltamethrin, including chromatid breaks, deletions, fragments and gaps was also observed. RT-PCR demonstrated significant up-regulation in testicular mRNA for glutathione-s-transferase and heat-shock protein-70 (HSP-70) whereas steroidogenic acute regulatory (StAR) mRNA was down-regulated after deltamethrin exposure. Oral administration of the biopesticide, under the condition of our study, was found to be safe when compared to the deleterious effect of deltamethrin in rats.

Experimental hypercholesterolemia and its modulation by some natural dietary supplements (pectin, garlic and ginseng) and by the drug gemfibrozil were studied. Experimental hypercholesterolemia was induced by feeding rabbits a 2% cholesterol-enriched diet for 28 days. Hypercholesterolemic rabbits were classified into five groups. One group did not receive treatments and served as a control hypercholesterolemic group. The other four groups were fed the cholesterol-enriched diet in conjunction with either 10% pectin, 2% garlic, 2% ginseng or 135 mg g-1 b.w gemfibrozil in a daily oral dose. A normal group of rabbits fed a plain chow diet was also included in the study. The hypolipidemic effect of the above treatments was examined by estimating serum triglycerides (TG), total-, LDL- and HDL-cholesterol. Post-heparin total and hepatic lipase activities were estimated in post-heparin plasma obtained 10 min after an intravenous injection of heparin (200 IU kg-1 b.w). In order to evaluate the antioxidant status of the rabbits, plasma malondialdehyde (MDA) level and erythrocyte superoxide dismutase (SOD) activity were measured. After killing, aorta from all rabbits were subjected to histopathological examination. Results of the study demonstrated that feeding the cholesterol-enriched diet caused a significant increase in total-, LDL-, and HDL-cholesterol, plasma MDA and post-heparin total and hepatic lipase activities. On the other hand, serum TG and erythrocyte SOD were not changed. Histopathological examination revealed marked alteration in the aortic wall with the appearance of large multiple atheromatous plaques. Both garlic and pectin were successful in a significant reduction of the hypercholesterolemia in a way comparable to gemfibrozil. Garlic was the only treatment that has antilipid peroxidative property. Erythrocyte SOD activity was not affected by hypercholesterolemia or by any of the treatments. Also, none of the treatments were able to modify the significant elevation of post-heparin lipolytic activities associated with the hypercholesterolemia or to significantly affect the serum triglycerides level. Finally, among the hypercholesterolemic groups that received treatments, the least changes in the aortic wall were shown in the animals of the gemfibrozil group. Slight degeneration was observed in the aorta of animals treated with pectin or garlic. Ginseng administration failed to exert any significant protection from the remarkable hypercholesterolemia or atherosclerosis associated with the cholesterol- enriched diet.