Relationships between serum selenium and zinc concentrations versus profibrotic and proangiogenic cytokines (FGF-19 and endoglin) in patients with alcoholic liver cirrhosis.

INTRODUCTION AND OBJECTIVE: Liver cirrhosis is a disease involving the liver parenchyma, which is characterised by fibrosis and impaired architectonics of the parenchyma with regenerative nodules. The aim of the study was to determine the relationship between stage of alcoholic liver cirrhosis, concentrations of selenium, zinc and profibrotic and proangiogenic cytokines (FGF-19, ENG). MATERIAL AND METHODS: The study included 99 patients with alcoholic cirrhosis and 20 healthy subjects. Ion chromatography with UV/VIS detection was used for determination of zinc ions in the previously mineralized serum samples. The measurements of selenium were performed with the ContrAA700 high-resolution continuum source graphite tube atomic absorption spectrometer. ELISA was used to determine concentration of FGF-19 and ENG in serum samples. RESULTS: Concentrations of zinc and selenium were significantly decreased in cirrhotic patients (p<0.001 for both). The highest concentration of FGF-19 was found in Child-Pugh stage C liver cirrhosis patients (806.9±650.3 pg/ml), and was significantly higher than observed in controls (p=0.005) and stage A patients (compensated cirrhosis) (p=0.02). The highest concentration of ENG was demonstrated in the control group (3.24±148 ng/ml) while the lowest in patients with decompensated cirrhosis (7.32±5.39 ng/ml and 7.92±4.18 ng/ml for stage B and C; p=0.03 and p=0.02, respectively). The use of the multiple-variable model demonstrated that the independent factors affecting the concentration of ENG were the concentration of bilirubin (p=0.02), INR (p=0.01) and duration of alcohol abuse (p=0.02). The independent determinants of FGF-19 concentrations were found to be the stage (severity) of liver cirrhosis (p=0.04) and INR (p=0.03). CONCLUSIONS: Concentrations of zinc and selenium in serum of patients with alcoholic liver cirrhosis are not independently related to concentrations of FGF-19 and ENG.

Analysis of plasma cytokines and angiogenic factors in patients with pretreated urothelial cancer receiving Pazopanib: the role of circulating interleukin-8 to enhance the prognostic accuracy.

BACKGROUND: Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients. METHODS: EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model. RESULTS: Increasing IL8(T1) level associated with lower response probability at covariance analysis (P=0.010). Both IL8(T0) (P=0.019) and IL8(T1) (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8(T1) best-predicted OS after backward selection. The NRI for this model was 39%.When analysed as a time-varying covariate, IL8(T1) level<80 pg ml(-1) portended significantly greater response (∼80%) and 6-month OS (∼60%) probability than level ≥ 80. CONCLUSION: IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability.

Effect of low-fat diets on plasma levels of NF-κB-regulated inflammatory cytokines and angiogenic factors in men with prostate cancer.

Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAF) in 145 men with prostate cancer enrolled in a preoperative, randomized controlled phase II trial with four arms: control (usual diet), low-fat (LF) diet, flaxseed-supplemented (FS) diet, and FS+LS diet. The mean duration of dietary intervention was 30 to 31 days. Among the individual arms, the largest number of significant changes (baseline vs. preoperative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (P < 0.05). Compared with the control arm, 6 CAFs-including proangiogenic factors (stromal-cell derived-1α) and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor)-all decreased in the LF arm compared with controls; three and four CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P < 0.001). The CAFs that changed in the LF arm are all known to be regulated by NF-κB, and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm but not in the FS-containing arms. These results suggest that a LF diet without flaxseed may reduce levels of specific inflammatory CAFs and suggests that the NF-κB pathway may be a mediator of these changes.

Antitumor and antiangiogenic activity of soy phytoestrogen on 7,12-dimethylbenz[alpha]anthracene-induced mammary tumors following ovariectomy in Sprague-Dawley rats.

Soy phytoestrogen is often used as hormone replacement therapy to alleviate the symptoms of menopause in postmenopausal women. Since estrogen has been considered as an important risk factor for the development of breast carcinoma, we need to know whether it is safe for these postmenopausal women with breast cancer to take soy foods that are rich in phytoestrogen. In the present study, we investigated the efficacy of soy phytoestrogen on tumor proliferation, apoptosis, and angiogenesis in mammary tumors that had already formed in ovariectomized rats. We found that soy phytochemical extraction inhibited proliferation and induced apoptosis in vitro and in vivo, and it demonstrated better antitumor effects than single phytoestrogen. Soy phytochemical extraction also produced surprisingly good antiangiogenic effects, which were evidenced by lower microvascular density, reduced plasma vascular endothelial growth factor, and increased plasma endostatin levels. Our findings suggest that soy phytochemical extraction exerts significant antitumor and antiangiogenic activity in a postmenopausal animal model with breast cancer.