Effect of mast cell stabilization on angiogenesis in primary and secondary experimental Trichinella spiralis infection.

BACKGROUND: Mast cells are known to affect the primary and secondary immune responses against parasites, and this effect is partially mediated through the release of pro-angiogenic mediators. The aim of this study was to explore the effect of the mast cell stabilizer (MCS), ketotifen, with and without albendazole, an anti-parasitic prescription medicine, on the inflammatory response against Trichinella spiralis, with the overall aim to investigate its effect on angiogenesis accompanying nurse cell formation. METHODS: The effect of ketotifen and albendazole was explored in eight groups of female BALB/c mice. Four groups were sensitized with a small dose of T. spiralis larvae. The drug regimen was then applied to both sensitized (challenged) and non-sensitized mice. The parasite load was assessed by histopathological examination of the small intestine and muscle tissue, and angiogenesis was assessed by immunohistochemistry to determine the expression of vascular endothelial growth factor (VEGF). RESULTS: Sensitized mice showed a significantly lower parasite load and a more pronounced inflammatory response than mice receiving a single infective dose of T. spiralis larvae. All treated groups showed a significant reduction in parasite count compared to the control groups (groups IAa and IBa), reaching approximately an 98.8% reduction in adult parasite count in the sensitized group treated with albendazole (groups IIAb and IIBb). MCS significantly decreased the parasite count during both the intestinal or muscular phases, reduced tissue inflammation, and decreased local VEGF expression, both in the non-sensitized and sensitized groups. CONCLUSION: Sensitization with a low dose of T. spiralis larvae was found to confer a partial protective immunity against re-infection and to positively affect the study outcomes, thus underlining the importance of vaccination, but after extensive studies. The anti-angiogenic effect of MCS protects against larval encystation during the muscle phase. The anti-angiogenic potential of albendazole suggests that the action of this anti-helminthic during trichinellosis is not confined to structural damage to the parasite cuticle but includes an effect on host immunopathological response.

Significance of Intracellular Adhesion Molecule-1 Polymorphism and IP-10 among Breast Cancer Patients.

Breast cancer (BC) is the second leading cause of women's death worldwide. Intercellular adhesion molecule-1 (ICAM-1) is involved in cell-cell interaction, migration and recruitment of immune cells. Polymorphisms in ICAM-1 gene may be involved in BC progression. IFN-gamma inducible protein-10 (IP-10) has the ability to recruit T-cells to induce cellular immunity and may have protective effect against BC development. The current study aimed to shed light on the role of of ICAM-1 SNP and/or serum levels of IP10 in BC in Egyptian female patients and detect possible correlation between these two factors and pathological prognostic markers. 40 breast cancer patients and 40 healthy females were enrolled in the study. Genotyping of ICAM-1 rs281437 SNP was done using real time PCR and serum levels of IP-10 were measured using ELISA. Allelic distribution demonstrated high frequency of ICAM-1 rs281437 CC genotype among BC patients (60%) compared to CT and TT alleles (30% and 10%, respectively). ICAM-1 rs281437 CC genotype showed 9.8 folds more risk to develop BC than other genotypes (95% CI=5.8-21.8, P<0.05). Relation between the studied alleles and hormonal receptors (ER, PR) showed that both ICAM-1 rs281437 CC and CT genotype have 5 folds more to be ER+, PR+ BC compared to TT allele (95% CI=0.21-117.8 and 0.15-125.4, respectively). Serum IP-10 levels were markedly decreased among breast cancer patients when compared with healthy controls (P = 0.001). In conclusion, ICAM-1 rs281437 CC genotype is significantly associated with breast cancer; females carrying CC allele may be at higher risk to develop BC than those carrying CT or TT genotypes. On the other hand, IP-10 may have a protective effect against breast cancer.