Effect of comorbidity on urinary neopterin in patients with breast carcinoma.

Urinary neopterin is increased in less than 20% of patients with breast carcinoma. Moderately increased neopterin concentrations are also known to accompany comorbid conditions commonly observed in patients with breast carcinoma, for example, diabetes mellitus or complications of atherosclerosis. In the present study, we evaluated the effect of the presence of comorbid conditions on urinary neopterin. A trend for higher neopterin concentrations was observed in patients with most of the comorbid conditions, but significantly higher neopterin was observed only in patients aged 70 years or older and in a heterogeneous group of patients with comorbidity other than diabetes mellitus, thyroid disorder, hyperlipidaemia, cardiac disorder or other malignancy. Significantly higher neopterin levels were noted in patients with two or more comorbid conditions. In conclusion, present data demonstrate an association between systemic immune activation reflected in increased urinary neopterin concentrations and age or presence of comorbid diseases in patients with breast carcinoma. A cumulative effect was observed with the presence of two or more comorbid conditions resulting in significantly increased urinary neopterin. These observations should be taken into account when interpreting the changes of parameters of systemic immune and inflammatory response in patients with breast carcinoma.

Urinary neopterin in patients with advanced colorectal carcinoma.

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 micromol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.

Phenotype and antitumor activity of ascitic fluid monocytes in patients with ovarian carcinoma.

Monocytes/macrophages (MO/MA) represent a major leukocyte population in the peritoneal cavity of patients with epithelial ovarian cancer (EOC). We examined the phenotypic characteristics and antitumor cell activity of ascitic MO in patients with EOC. MO/MA phenotype was compared with MO in peripheral blood by two- and three-color flow cytometry. Cytotoxic/cytostatic effects of different cytokines on cultured EOC cells were measured by initial labeling or uptake inhibition of [methyl-3H] thymidine. Malignant ascites had higher proportion of MO/MA with the CD14brightCD16+ phenotype than peripheral blood. Cell surface antigen expression of activation and differentiation in peripheral blood and ascites, including CD38, CD40, CD64, and CD86, was higher on CD14brightCD16- and CD14brightCD16+ than on CD14dimCD16- cells. HLA-DR expression was higher on ascitic MO/MA than peripheral blood MO. Significant cytotoxic/cytostatic activity was elicited by treating ascitic MO/MA with interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), but not with interleukin-12, paclitaxel, granulocyte-monocyte colony-stimulating factor (GM-CSF), or tumor necrosis factor-alpha (TNF-alpha). Soluble CD40Lt did not enhance MO/MA cytotoxic activity, and inhibited IFN-gamma or IL-2 induced cytoxicity. We conclude that MO/MA from ascites have elevated proportions of CD14brightCD16+ cells, showing phenotypic features of activation. IFN-gamma induces the cytotoxic and cytostatic activity of MO/MA that is inhibited by CD40Lt.