Assessment of the pathway of apoptosis involving PAR-4, DAXX and ZIPK proteins in CLL patients and its relationship with the principal prognostic factors

Par-4 (prostate apoptosis response-4) protein was originally found upregulated in prostate tumor cells undergoing apoptosis. Then it was further identified as a proapoptotic protein upregulated both in normal and leukemic lymphocytes. The aim of our study was to assess PAR-4 protein expression in the B cells of CLL patients and to examine its relationship with the expression of other proteins involved in the apoptosis process, such as DAXX, ZIPK and BCL-2. We found a positive relationship between PAR-4 and BCL-2 protein expression. Additionally, there was a positive correlation between PAR-4 and both DAXX and ZIPK protein expression. The results of our research were also analyzed in association with the principal CLL prognostic factors. There was a positive correlation between the expression of PAR-4 protein and the lactate dehydrogenase (LDH) serum concentration (p < 0.005). The expression of PAR-4 protein in B cells correlated positively with the percentage of CD38+ cells (p < 0.05), as well as with CD38+/ZAP-70+ cells (p < 0.05). Moreover, we found a close relationship between LPL protein expression or LPL/ADAM29 MFI ratio and PAR-4 protein expression. Our results confirm the significance of apoptosis deregulation in CLL, and suggest a possible relationship between PAR-4 expression and the clinical course of the disease. This however requires further investigation. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 98&#8211;103

CD3+/CD16+CD56+ cell numbers in peripheral blood are correlated with higher tumor burden in patients with diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma is the commonest histological type of malignant lymphoma, andremains incurable in many cases. Developing more efficient immunotherapy strategies will require betterunderstanding of the disorders of immune responses in cancer patients. NKT (natural killer-like T) cells wereoriginally described as a unique population of T cells with the co-expression of NK cell markers. Apart fromtheir role in protecting against microbial pathogens and controlling autoimmune diseases, NKT cells havebeen recently revealed as one of the key players in the immune responses against tumors. The objective of thisstudy was to evaluate the frequency of CD3+/CD16+CD56+ cells in the peripheral blood of 28 diffuse largeB-cell lymphoma (DLBCL) patients in correlation with clinical and laboratory parameters. Median percentagesof CD3+/CD16+CD56+ were significantly lower in patients with DLBCL compared to healthy donors(7.37% vs. 9.01%, p = 0.01; 4.60% vs. 5.81%, p = 0.03), although there were no differences in absolute counts.The frequency and the absolute numbers of CD3+/CD16+CD56+ cells were lower in advanced clinical stagesthan in earlier ones. The median percentage of CD3+/CD16+CD56+ cells in patients in Ann Arbor stages 1–2 was5.55% vs. 3.15% in stages 3–4 (p = 0.02), with median absolute counts respectively 0.26 G/L vs. 0.41 G/L (p == 0.02). The percentage and absolute numbers of CD3+/CD16+CD56+ cells were significantly higher in DL-BCL patients without B-symptoms compared to the patients with B-symptoms, (5.51% vs. 2.46%, p = 0.04;0.21 G/L vs. 0.44 G/L, p = 0.04). The percentage of CD3+/CD16+CD56+ cells correlated adversely with serumlactate dehydrogenase (R= –445; p < 0.05) which might influence NKT count. These figures suggest a relationshipbetween higher tumor burden and more aggressive disease and decreased NKT numbers. But it remains tobe explained whether low NKT cell counts in the peripheral blood of patients with DLBCL are the result of theirsuppression by the tumor cells, or their migration to affected lymph nodes or organs

Association of Serum Adiponectin, Leptin, and Resistin Concentrations with the Severity of Liver Dysfunction and the Disease Complications in Alcoholic Liver Disease

Background and aims. There is growing evidence that white adipose tissue is an important contributor in the pathogenesis of alcoholic liver disease (ALD). We investigated serum concentrations of total adiponectin (Acrp30), leptin, and resistin in patients with chronic alcohol abuse and different grades of liver dysfunction, as well as ALD complications. Materials and Methods. One hundred forty-seven consecutive inpatients with ALD were prospectively recruited. The evaluation of plasma adipokine levels was performed using immunoenzymatic ELISA tests. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Results. Acrp30 and resistin levels were significantly higher in patients with ALD than in controls. Lower leptin levels in females with ALD compared to controls, but no significant differences in leptin concentrations in males, were found. High serum Acrp30 level revealed an independent association with advanced liver dysfunction, as well as the development of ALD complications, that is, ascites and hepatic encephalopathy. Conclusion. Gender-related differences in serum leptin concentrations may influence the ALD course, different in females compared with males. Serum Acrp30 level may serve as a potential prognostic indicator for patients with ALD

The Increase of Circulating PD-1- and PD-L1-Expressing Lymphocytes in Endometriosis: Correlation with Clinical and Laboratory Parameters

The cause of endometriosis remains unknown. However, studies investigating the link between this condition and the immune system revealed several immunological abnormalities focused on cell-mediated immunity. As a major immune checkpoint, programmed cell death protein 1 (PD-1) displays an important inhibitory function in the maintenance of peripheral tolerance. The expression of PD-1 and its ligand (PD-L1) may contribute to continuous T cell activation and development of inflammation and injury of the tissue. To our knowledge, this is the first study evaluating frequencies of PD-1-positive T CD3+ cells (CD4+ and CD8+) and B cells (CD19+) in patients with endometriosis. Peripheral blood (PB) samples from 25 female patients and 20 healthy age and sex-matched subjects serving as controls were used in the study. Using flow cytometric analysis, we assessed the differences in the frequencies of PD-1-positive T and B lymphocytes in the study group and healthy individuals. Alteration of the PD-1/PD-L1 axis may contribute to the pathogenesis of endometriosis, as patients with advanced disease are characterized by higher frequencies of PD-1-positive T and B cells. Expression of PD-1 and PD-L1 on T and B cells could represent the hallmark of immune system reaction to chronic antigenic exposition in patients with endometriosis

Expression of angiogenesis-stimulating factors (VEGF, CD31, CD105) and angiogenetic index in gingivae of patients with chronic periodontitis

The aim of this study was to determine the prognostic value of the angiogenesis rate in chronic periodontitis(CP). A total of 61 human gingival samples were taken from patients with CP (n = 40) obtained duringopen curettage with gingivectomy, healthy periodontia (n = 15), and reactive lymph nodes (n = 7). Quantitativeimmunocytochemistry studies of VEGF, CD31 (PECAM-1) and CD105 (endoglin) were performed using thespatial visualization method. CD105/CD31 and VEGF/CD31 angiogenetic ratios (ARs) were established todetermine the proliferation fraction of the endothelium. In patients with CP, the proliferation of blood vesselswas observed, including the presence of numerous high endothelial venules (HEVs) and ordinary vessels. Ingingival HEVs of patients with CP, the higher expression was shown by CD31 and, in turn CD105 and VEGF.The entire vascular expression of CD31 in the gingiva correlates with grading in lamina propria, but our studyfailed to document correlations between the expression of VEGF and CD105 and clinical data of patients withCP. Higher ARs were seen in gingivae of CP patients compared to controls. We concluded that overexpressionof the angiogenesis-associated factors in CP suggests its significance in protracting the inflammatory process orperiodic exacerbations of the process and destruction of the periodontium. The increased CD105/CD31 andVEGF/CD31 ratios in gingiva confirms an augmented proliferative fraction of the endothelium in gingiva withCP

Angiogenesis-Related Biomarkers in Patients with Alcoholic Liver Disease: Their Association with Liver Disease Complications and Outcome

Angiogenesis is believed to be implicated in the pathogenesis of alcoholic liver disease (ALD). We aimed to explore the usefulness and accuracy of plasma angiogenic biomarkers for noninvasive evaluation of the severity of liver failure and ALD outcome. One hundred and forty-seven patients with ALD were prospectively enrolled and assessed based on their (1) gender, (2) age, (3) severity of liver dysfunction according to the Child-Turcotte-Pugh and MELD scores, and (4) the presence of ALD complications. Plasma levels of vascular endothelial growth factor (VEGF-A) and angiopoietins 1 and 2 (Ang1 and Ang2) were investigated using ELISAs. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Significantly higher concentrations of Ang2 and VEGF-A in ALD patients as compared to controls were found. There was no difference in Ang1 levels in both groups. A positive correlation of Ang2 levels with INR (Rho 0.66; P<0.0001) and its inverse correlation with plasma albumin levels (Rho –0.62; P<0.0001) were found. High Ang2 concentrations turned out to be an independent predictor of severe liver dysfunction, as well as hepatic encephalopathy and renal impairment. Ang2 possessed the highest diagnostic and prognostic potential among three studied angiogenesis-related molecules