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In the present study, we determined complex indices of inflammatory activity and compared the performance of these indices as prognostic biomarkers in a cohort of breast cancer patients. All proposed composite biomarkers could be evaluated in 418 out of 474 patients in the cohort with complete data on peripheral blood cell count, urinary neopterin, albumin and C-reactive protein. Neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, Glasgow prognostic index, modified Glasgow prognostic index, prognostic nutritional index and C-reactive protein/albumin ratio were calculated and further complex indices were proposed. Although a number of the investigated indices were significantly associated with survival in the univariate analysis, only age and stage, but none of the laboratory biomarkers or composite biomarkers, were significant predictors of survival in the whole group in the multivariate analysis. In patients evaluated before the start of the treatment, age, stage and urinary neopterin were significant predictors of survival. These results underscore the importance of neopterin as a prognostic biomarker in breast cancer.

The aim of the present study was to investigate the association of peripheral-blood cell count (PBC)-derived ratios, other biomarkers of inflammation and biomarkers of tumor growth with outcome in a cohort of patients presenting for the next line of therapy after the failure of prior systemic treatment. The data of 51 patients with advanced/metastatic colorectal carcinoma treated with cetuximab in the second or higher line of therapy were retrospectively analyzed. The median duration of cetuximab therapy and the median survival were 5.1 and 12.1 months, respectively. C-reactive protein (CRP), but not urinary neopterin correlated significantly with PBC-derived ratios. Both CRP and urinary neopterin correlated positively with carcinoembryonic antigen (CEA) concentrations and biomarkers of liver dysfunction. Although a number of parameters predicted overall survival in univariate analysis, only hemoglobin, CEA change and serum bilirubin were independent predictors of survival. In conclusion, in patients with metastatic colorectal carcinoma and predominantly liver metastases, the outcome of therapy in the advanced line setting was associated with initial hemoglobin level, a decrease of CEA concentration and initial presence of liver dysfunction. Urinary neopterin did not correlate with PBC-derived ratios, in contrast to CRP, but both urinary neopterin and serum CRP concentrations correlated with laboratory parameters of liver dysfunction.

New spectrum of side effects has emerged with the introduction of targeted therapies, including changes in parameters determining cardiovascular risk. Among other laboratory parameters, hyperuricemia and elevated Creactive protein (CRP) are associated with increased risk of cardiovascular disease. The aim of the present study was to investigate the changes of serum uric acid and CRP during the therapy with cetuximab, combined with 5- fluorouracil and high-dose folinic acid, in patients with metastatic colorectal carcinoma and the association of these changes with the outcome of the therapy. CRP and uric acid were determined using particle-enhanced immunoturbidimetric assay and uricase method, respectively. Measurements before and during the treatment were compared by Wilcoxon signed rank test, and comparison between survivors and non-survivors was performed by Mann-Whitney U test. Compared to baseline (pre-treatment) concentrations, serum uric acid was decreased significantly throughout the course of the combination treatment with irinotecan, 5-fluorouracil, highdose folinic acid and cetuximab. The decrease was evident early in the course of treatment. Serum CRP was also decreased significantly throughout the most of the course of therapy. The significant decrease of serum uric acid and CRP was evident already one week after the start of treatment. Serum CRP was significantly lower in patients who survived 12 months, but no difference of uric acid concentrations between survivors and non-survivors was found. A marked decrease of serum uric acid was observed during the combination therapy. High CRP was associated with poor prognosis, but no association between uric acid and prognosis was noted.

Monocytes/macrophages are thought to play a fundamental role in the development of vascular lesions in atherosclerosis. In the present study, we evaluated circulating CD14+CD16+ monocytes, laboratory parameters of the risk of atherosclerosis, including serum cholesterol, homocysteine and C-reactive protein, urinary neopterin, serum a-tocopherol and retinol along with carotid intima-media thickness in patients with breast carcinoma. A significant correlation was observed between the absolute numbers of CD14+CD16+ monocytes, serum HDL cholesterol and triglyceride concentrations. In conclusion, present data extend the observation of an association between peripheral blood CD14+CD16+ monocyte counts and lipid metabolism to cancer patients. No correlation of CD14+CD16+ monocyte counts with urinary neopterin concentrations was observed.

Bevacizumab, monoclonal antibody targeting vascular endothelial growth factor, is effective in different tumors, including colorectal carcinoma, non-small cell lung cancer, renal cell carcinoma and breast cancer. Increased serum or urinary concentrations of neopterin, an indicator of systemic immune response, have been described in patients with tumors of different primary locations, and further increase has been observed during anticancer therapy. An increase of urinary neopterin has been described after administration of cytokines, cytotoxic chemotherapy, or external beam radiation, but less is known about the effects of targeted agents on systemic immune response. We have studied serum homocysteine, C-reactive protein, α-tocopherol and retinol, and urinary neopterin in patients with metastatic breast cancer treated with bevacizumab, taxane and carboplatin. Homocysteine and C-reactive protein were determined immunochemically. α-tocopherol, retinol and urinary neopterin were determined by high performance liquid chromatography. Homocysteine, C-reactive protein and urinary neopterin decreased, while retinol and α-tocopherol increased during the therapy. In conclusion, the treatment of patients with metastatic breast cancer with bevacizumab, taxane and carboplatin resulted in the suppression of systemic inflammatory and immune response. The suppression of systemic inflammatory and immune response was associated with an increase in serum vitamin concentrations.

Introduction: High indoxyl sulfate (IS) concentration is a serious problem for patients with CKD increasing the risk of cardiovascular diseases and CKD progression. Thus, the methods of decreasing the toxin concentrations are highly desired. The study aimed to discover the role of selected intestine-related factors on IS concentration. Methods: We evaluated the impact of ABCG2 and ABCC2 polymorphisms influencing activity and protein intake by normalized protein catabolic rate. Additionally, we examined the relation of IS and uric acid (UA) that can share common elimination transporters. A monocentric, prospective, open cohort pilot study was performed on 108 patients undergoing dialysis treatment. Results: The positive effect of residual diuresis on the reduction of IS levels was confirmed (p = 0.005). Also, an increase in IS depending on the dietary protein intake was confirmed (p = 0.040). No significant correlation between ABC gene polymorphisms was observed either, suggesting the negligible role of ABCG2 and ABCC2 in the elimination of IS in small bowel. The significant difference was observed for UA where ABCG2 421C>A (rs72552713) gene polymorphism was higher (505.3 μmol/L) in comparison with a wild-type genotype (360.5 μmol/L). Conclusion: No evidence of bowel elimination pathway via ABCC2 and ABCG2 transporters was found in renal replacement therapy patients. [ABSTRACT FROM AUTHOR]

Abstract Background Combination of platinum derivatives with paclitaxel is currently the standard front line regimen for patients with epithelial ovarian carcinoma, and represents also an active regimen in patients with metastatic breast or unknown primary carcinomas. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal mucositis induced by chemotherapy, but little is known about intestinal permeability in patients treated with paclitaxel or platinum. Methods Intestinal permeability was assessed in 36 breast and ovarian cancer patients treated with paclitaxel/platinum combination by measuring, using capillary gas chromatography, urinary sucrose, lactulose, xylose and mannitol after oral challenge. The significance of differences during the therapy compared to pre-treatment values was studied by Wilcoxon paired test. The differences between groups of patient were studied by Mann-Whitney U test. Fisher exact test was used to compare the frequency in different subgroups. Results After administration of the first dose, a significant (p < 0.05) decrease in xylose absorption and increased lactulose/mannitol, sucrose/mannitol, lactulose/xylose and sucrose/xylose ratios were observed, but these parameters returned subsequently to pre-treatment levels. Patients who experienced serious (grade 3 or 4) toxicity had at baseline significantly lower percentages of xylose, mannitol and sucrose, and higher lactulose/mannitol ratio. Nine of 13 (69%) patients with baseline lactulose/mannitol ratio 0.070 or above experienced serious toxicity compared to 4 out of 23 patients (17%) with the ratio below 0.070 (p = 0.002). Post-treatment lactulose, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were significantly increased in patients with serious toxicity. Conclusion A transient significant increase in lactulose/monosaccharide and sucrose/monosaccharide ratios was observed in ovarian and breast cancer patients treated with paclitaxel and platinum. Increased lactulose absorption, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were evident in patients with grade 3 or 4 toxicity, and increased baseline lactulose/mannitol ratio predicted serious toxicity.