Serum evaluation of angiogenic cytokine basic fibroblast growth factor, hepatocyte growth factor and TNF-alpha in patients with myelodysplastic syndromes: correlation with bone marrow microvascular density.

Recent studies have documented that angiogenesis plays a significant role in haematological malignancies, including mylodysplastic syndromes (MDS). Basic fibroblast growth factor (b-FGF), Hepatocyte growth factor (HGF) and Tumor necrosis factor-alpha (TNF-alpha) are multifunctional cytokines that potently stimulate angiogenesis. The aim of the present study was to evaluate the microvascular density (MVD) and the serum levels of these angiogenic factors in patients with myelodysplastic syndromes (MDS). In 61 patients with MDS, MVD was measured in bone marrow biopsies and b-FGF, HGF and TNF-alpha were determined in the serum of the same patients by enzyme-linked immunosorbent assay (ELISA). Serum levels of b-FGF, HGF and TNF-alpha as well as MVD in the bone marrow were increased in MDS patients compared to healthy controls (p<0.0001). Levels of b-FGF, HGF and TNF-alpha were also significantly higher in high-risk for leukemic transformation MDS than in low-risk (p<0.0001). Significant differences were also found regarding MVD in high and low risk patients (p<0.001). Both b-FGF and HGF levels were significant predictors of survival (p<0.0005, log-rank test). The present study showed that serum levels of b-FGF, HGF and TNF-alpha are significantly increased and dependent on the severity of MDS suggesting that the determination of these parameters may offer considerable information regarding disease progression and prognosis.

Potential role of soluble angiopoietin-2 and Tie-2 in patients with inflammatory bowel disease.

BACKGROUND: Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD). MATERIALS AND METHODS: Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease. RESULTS: Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0.05 and P < 0.001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0.04) median serum Ang-2 levels but significantly lower (P = 0.02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0.02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin. CONCLUSIONS: Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD.

Altering interface detector positioning in combination with prestorage filtration to achieve a better quality of single donor platelet concentrates using the CS 3000 Plus blood separator.

The interface detector (ID) is an optical density sensor that affects the quality of single donor platelet collection using the CS 3000 Plus blood separator. The purpose of this study was to evaluate the effect of altering ID position on platelet yields and the contamination of leukocytes (WBC) in platelet concentrates (PCs). Dual-needle apheresis procedures (n = 93) were performed using an A35 collection chamber. Plateletpheresis products were separated according to interface detector offset (IDO) positioning into four groups: A: IDO = 6 (n = 33), B: IDO = 10 (n = 28), C: IDO = 12 (n = 18), D: IDO = 18 (n = 14). For 32% of the collections, the closed system apheresis kit with integral Sepacell filter (Baxter) was used and 33% of them were leukodepleted using the LRP-6 (PALL) filter. Our results showed that: (1) Although the mean blood volume and the time of apheresis were significantly higher, the mean platelet (PLT) yields were significantly lower in PCs of group A as compared to all other groups (P < 0.0001). (2) The mean WBC content was significantly higher in PCs of group D as compared to all other groups (P < 0.0001). (3) With the LRP-6 filter, a significantly higher WBC reduction as well as PLT loss in PCs was observed as compared to Sepacell leukapheresis filter. A higher PLT loss was observed with both filters when leukoreduction was performed within the first 6 hours as compared to 24 hours after the procedure. Conclusively, an IDO setting of 10 or 12 results in better platelet yields in PCs without increasing the WBC contamination. An IDO positioning of 18 or higher must be avoided or should be always combined with PCs leukodepletion. Finally, the best timing for leukoreduction is 24 hours after the plateletpheresis.

Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: correlation with markers of disease activity.

Hepatocyte growth factor (HGF) has been shown to be involved in angiogenesis, epithelial cell proliferation, and osteoclast activation. HGF and its receptor are expressed on myeloma cell lines and could be involved in the pathogenesis of bone destruction in multiple myeloma (MM). The aim of this study was to examine serum levels of HGF in untreated MM patients and its correlation with bone turnover indices and markers of disease activity. Forty-seven newly diagnosed MM patients and 25 controls were included: 12 patients were of stage I, 13 of stage II, and 22 of stage III (Durie-Salmon classification). Bone lesions were scored from 0 to 3, according to X-ray findings. Serum osteocalcin (OC), interleukin-6 (IL-6), TNF-alpha, beta(2)-microglobulin (beta(2)M), CRP, calcium, and 24-hr urine N-telopeptide cross-links of collagen breakdown (NTx) were determined. HGF levels were significantly higher at stage III compared to stages II and I (medians: 1,990.4 vs. 1,743.8 and 1,432.4 pg/mL, respectively, P < 0.05). Similarly, NTx, IL-6, TNF-alpha, CRP, beta(2)M, and calcium increased significantly with advancing stage (P < 0.01). OC was higher at stage I in comparison to stages II and III (P < 0.01). All parameters were significantly higher in patients than controls. HGF showed a strong correlation with IL-6 and TNF-alpha and less with beta(2)M, CRP, NTx, and OC. We conclude that serum HGF levels are increased in advanced stages of MM disease and extended bone lesions. HGF correlates with IL-6 and TNF-alpha, which are cytokines involved in osteoclast stimulation in MM. However, an independent association of HGF with bone turnover markers was not shown in this study, thus its role in MM bone disease needs to be further clarified.