Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping.

Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand-2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings.

Activation-induced apoptosis in peripheral blood mononuclear cells during hepatosplenic Schistosoma mansoni infections.

It is well established that programmed cell death (apoptosis) is an important regulator of host responses during infection with a variety of intra- and extra-cellular pathogens. The present work aimed at assessment of in vitro spontaneous and phytohemagglutinin (PHA)-induced apoptosis in mononuclear cells isolated from patients with hepatosplenic form of S. mansoni infections. Cell death data were correlated to the degree of lymphoproliferative responses to PHA as well as to the serum anti-schistosomal antibody titers. A markedly significant increase in PHA-induced apoptosis in lymphocytes isolated from S. mansoni-infected patients was seen when compared to the corresponding healthy controls. However, a slight difference was recorded between the two studied groups regarding the spontaneous apoptosis. This was accompanied with a significant impairment of in vitro PHA-induced lymphoproliferation of T cells from S. mansoni patients. Data of the present study supports the hypothesis that activation-induced cell death (AICD) is a potentially contributing factor in T helper (Th) cell regulation during chronic stages of schistosomiasis, which represents a critically determinant factor in the host-parasite interaction and might influence the destiny of parasitic infections either towards establishment of chronic infection or towards host death.

IL-1, IL-4 production and IgE levels in acute and chronic fasciolosis before and after triclabendazole treatment.

IL-1 generation by mononuclear phagocytes, IL-4 production by Th2 lymphocytes and IgE levels in serum were measured in eight patients with acute fasciolosis and seven patients in the chronic stage of the disease before and after triclabendazole treatment. Results were compared with those of a control group of ten individuals. The monocytes and lymphocytes from patients with acute and chronic fasciolosis produced significantly lower levels of IL-1 and IL-4 respectively, particularly in the chronic phase of the disease, as compared to the control. A significant increase in IgE level in both acute and chronic fasciolosis was observed. The level was significantly higher in acute as compared to chronic cases. After treatment with triclabendazole IL-1, IL-4 and IgE levels moved towards the control indicating obvious improvement in the immunological responses of the patients.

High prevalence of islet cell antibody and defective insulin release in children with schistosomiasis.

The importance of islet cell antibodies (ICA) as a predictor of insulin dependent diabetes mellitus (IDDM) has been emphasized by several investigators since 1974. The ICA was also detected in patients with various immune-mediated diseases such as auto-immune thyroiditis. Schistosomiasis is a wide-spread helminthic disease which affects more than 200 million patients all over the world. Immunological abnormalities and pancreatic affection are features of the disease. We studied the prevalence of ICA in 40 children with schistosomiasis (20 males and 20 females), 14 children with IDDM, and 30 of the non-diabetic siblings of patients with IDDM, and evaluated the oral glucose tolerance and early release of insulin after an i.v. load of glucose in children with schistosomiasis, diabetics' siblings, and 10 normal age-matched controls. The age of onset of IDDM and duration of the disease were 6.5 +/- 2.3 and 4.1 +/- 1.2, respectively, and the age of onset and duration of schistosomiasis were 8.3 +/- 2.7 and 2.5 +/- 1.5 years, respectively. Sex, consanguinity, history of previous virus diseases (mumps, measles and rubella), and sex maturity rating did not differ among the three study groups; however, children with schistosomiasis were significantly older. The prevalence of ICA was 50 per cent in children with IDDM, 13 per cent in the diabetics' siblings, and 25 per cent of children with schistosomiasis. Glucose tolerance was normal in children with schistosomiasis and diabetics' siblings. Early release of insulin after i.v. glucose load was significantly lower in children with schistosomiasis compared to the other two groups. In conclusion, the high prevalence of ICA and the decreased early release of insulin in response to an i.v. glucose load in children with schistosomiasis suggest that auto-immune aggression against the islet cells contributes in the pathogenesis of pancreatic disease in these patients, and might increase the risk for developing glucose intolerance and diabetes.

Diagnostic significance of Schistosoma mansoni proteins Sm31 and Sm32 in human schistosomiasis in an endemic area in Egypt.

We performed a series of ELISAs to evaluate the diagnostic significance of two Schistosoma mansoni proteins, Sm31 (cysteine proteinase, cathepsin B) and Sm32 (asparaginyl endopeptidase). Our study populations were chosen from two villages in an endemic area close to Alexandria. Using fusion proteins MS2-Sm31 and MS2-Sm32 as antigens, 70% and 78.9%, respectively, of patient sera from 134 parasitologically confirmed cases reacted positively. The percentage of seropositivity increased to 84.5% when parasite-derived proteins Sm31 and Sm32 were used. The serum levels of antibodies to these two proteins in recombinant or native forms do not correlate with intensity of infection and hence are detected even when egg counts are low, which makes proteins Sm31 and Sm32 useful antigens in the identification of S. mansoni infected cases, particularly in endemic areas in Egypt.