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D Wolowiec

Publications and source records attributed to D Wolowiec.

10 recordsLinked to original sources
PubMed2006

sVE-cadherin and sCD146 serum levels in patients with multiple myeloma.

The role of angiogenesis in multiple myeloma (MM) pathogenesis is well established. Angiogenesis is linked to the functional state of endothelial junctions that are modulated by the growth and activation of endothelial cells. CD146 and vascular endothelial-cadherin (VE-cadherin) are cell adhesion molecules localized at the endothelial junction. The aim of the study was to assess sVE-cadherin and sCD146 serum levels in MM patients. Forty-six untreated patients with MM were included in this study. In addition, 23 of 46 patients were analyzed again in partial remission after initial chemotherapy. Twenty-two samples from healthy volunteers were evaluated as the control. There was no significant difference in sCD146 level between MM patients and the control (511 +/- 177.2 vs. 460.9 +/- 156.9 ng/ml respectively). In untreated MM patients, sVE-cadherin level was significantly higher than in the control (1.36 +/- 0.55 vs. 0.63 +/- 0.56 ng/ml respectively; P < 0.05). In untreated MM patients, sVE-cadherin level was significantly higher than in MM patients in partial remission (1.36 +/- 0.55 vs. 0.5 +/- 0.33 respectively; P < 0.05). sVE-cadherin but not sCD146 serum level was increased in untreated MM patients and decreases after chemotherapy in patients in partial remission. VE-cadherin may reflect intensity of angiogenesis in MM and may be useful in prognosis of response to treatment.

Aged↗
PubMed2004

Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia.

In the present study, we have examined the kinetics and magnitude of expression of the CD28 and CD152 molecules on unstimulated and anti-CD3+rIL-2-stimulated peripheral blood CD4+ and CD8+ T cells in patients with chronic lymphocytic leukaemia (B-CLL) and controls. The mean percentages of both CD3+/CD4+/CD28+ and CD3+/CD8+/CD28+ cells were significantly lower in B-CLL than in controls before culture, decreased rapidly, reaching their lowest levels between 24 and 48 h, and returned to basal levels after 72 h of culture. In controls, the lowest proportions of CD3+/CD4+/CD28+ and CD3+/CD8+/CD28+ cells were found after 24 h and returned to prestimulation levels after 48 h of stimulation. We observed significantly higher proportions of unstimulated CD3+/CD4+/CD152+ and CD3+/CD8+/CD152+ cells in B-CLL patients than in controls. The highest percentages of CD3+/CD4+/CD152+ and CD3+/CD8+/CD152+ cells were observed in controls after 72 h, and in B-CLL patients after 24 h, and remained statistically higher after 48, 72 and 96 h of stimulation. CD152 molecule expression returned to prestimulation levels after 96 h of culture in controls, and after 120 h in B-CLL patients. The abnormal kinetics and levels of CD28 and CD152 expression on T cells in B-CLL may lead to a state of hyporesponsiveness or anergy and could be one of the mechanisms of immune deficiency in this disease.

Adult↗
PubMed2001

p16(INK4a) and p15(INK4b) gene methylations in plasma cells from monoclonal gammopathy of undetermined significance.

p15(INK4b) and p16(INK4a) proteins are cell cycle regulators involved in the inhibition of G1 phase progression. High frequency of methylation of both genes has been reported in multiple myeloma (MM), but it remains to be determined how and when these alterations contribute to tumorigenesis. Monoclonal gammopathy of undetermined significance (MGUS) represents an early disease stage in a fraction of MMs. Plasma cells from 33 patients with MGUS and 33 patients with MM were isolated and analyzed for p15(INK4b) and p16(INK4a) methylation by methylation-specific polymerase chain reaction. Selective methylation was found in 19% for p16(INK4a), 36% for p15(INK4b), and 6.5% for both genes in MGUS, and frequencies were similar in MM suggesting that methylation of these genes is an early event, not associated with transition from MGUS to MM. p15(INK4b) and p16(INK4a) gene methylation might contribute to immortalization of plasma cells rather than malignant transformation in the natural history of MM.

Adult↗
PubMed2001

Cell cycle regulatory proteins and apoptosis in B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: The pathogeny of B-cell chronic lymphocytic leukemia (B-CLL) involves both deregulated proliferation and inhibition of cell death. A particular role in the regulation of these phenomena is played by proteins involved in early G1 phase regulation: pRb kinases: cyclin-dependent kinases (cdk): cdk4 and cdk6 activated by cyclins D, and universal cdk inhibitor p27(Kip1). DESIGN AND METHODS: We determined by flow cytometry the expression of p27(Kip1) and cyclins D (D2 and D3) in populations of peripheral blood lymphocytes obtained from 59 (for p27(Kip1)) and 31 (for cyclins D) previously untreated patients with B-CLL, and compared them with cell cycle parameters, cell viability and apoptosis in 72-hour cultures in medium only. As a control we determined the expression of p27(Kip1), cyclin D2 and D3 in peripheral blood CD5+/CD19+ lymphocytes from 15 healthy donors. RESULTS: p27(Kip1) was present in nearly 100% of lymphocytes in all B-CLL populations tested. Its cellular content estimated semiquantitatively by specific mean fluorescence intensity was higher than in normal CD5+/CD19+ lymphocytes, p27(Kip1) was inversely correlated with patients' age and not correlated with other clinical variables, cell cycle or apoptosis rate. Cyclin D2 was detectable in 25 out of 31, and cyclin D3 in all B-CLL lymphocytes populations studied. In contrast to p27Kip1 present in all CD5+/CD19+ lymphocytes, both cyclins were detected only in a subset of neoplastic cells: 27.5 to 87% (mean 51.2) for cyclin D2 and 20.3 to 98% (mean 76.5) for cyclin D3. In cyclin D2- and D3-positive normal CD5+/CD19+ lymphocytes and B-CLL cell populations, cyclin D3 was expressed in a higher percentage of cells than cyclin D2. Both cyclin D2-and cyclin D3-positive fractions of B-CLL cells were, on average, larger than corresponding fractions of normal CD5+/CD19+ peripheral blood lymphocytes. INTERPRETATION AND CONCLUSIONS: Our results indicate that cyclin D3 plays an important role in the regulation of normal and neoplastic CD5+/CD19+ cells, and point to the possibility of the exit of a number of CLL lymphocytes from quiescence.

Adult↗
PubMed1999

CDK1 and cyclin A expression is linked to cell proliferation and associated with prognosis in non-Hodgkin's lymphomas.

Cellular proliferation is regulated by several kinasic complexes associating cyclins and their catalytic subunits cyclin-dependent kinases (CDKs). In order to gain insight into the mechanisms underlying proliferation in non-Hodgkin's lymphoma (NHL), we examined the expression of certain cell cycle regulatory proteins normally expressed in lymphoid cells, cyclins A, B, D3 and E and cdk1, 2, 4, and 6. In 70 patients presenting a previously untreated lymphoma, cyclins and CDKs were studied by Western blotting and quantified by densitometry. Flow cytometry study of DNA content was carried out for all patients in order to study cell proliferation and level of ploidy. The results were analysed according to the histological types, the immunological phenotypes of the lymphomas and the outcome of the patients. Cdkl and cyclin A were correlated with the percentage of cells in S and S+G2/M phases, and significantly different according to the grade of malignancy, with the lowest expression in low-, and the highest in high-grade NHL according to the Working Formulation. In B-NHLs, cdk1, cyclin A, as well as cdk2, cyclin D3 and E expression was higher in the aneuploid than in the euploid group. Our results point to some particularities of cell cycle regulation in two lymphoma sub-types: 1) a low expression of cyclin D3 and cdk6 in mantle cell lymphomas and 2) a discrepancy between the high proliferative activity and the level of protein expression in Burkitt's lymphomas. CDK1 and cyclin A showed a significant prognostic value for achievement of complete remission (Cdk 1) and for both disease free (cyclin A) and overall survival (cyclin A and cdk1): low protein level was associated with the best prognosis in B-NHLs. Our results show that differential cell cycle regulating protein expression may be associated with different biological and clinical behaviour of NHLs and confirm the usefulness of the study of cell cycle regulation as a tool for understanding lymphoid malignancies.

Adolescent↗
PubMed1995

Plasma cell proliferation in monoclonal gammopathy: relations with other biologic variables--diagnostic and prognostic significance.

PURPOSE: We investigated the place of direct plasma cell proliferation analysis beside other biologic data in monoclonal gammopathy, particularly the serum level of C-reactive protein (C-RP) PATIENTS: Eighty patients were studied at the time of their diagnosis. Patients with a serum creatinine level greater than 200 mumol/L were excluded. METHODS: Plasma cell proliferation analysis was performed after bromodeoxyuridine incorporation and double immunoenzymatic labeling on cytological smears, making determination of the plasma cell labeling index (LI) possible. The other biologic variables studied were related to tumor burden (plasmacytosis, hemoglobin, serum levels of monoclonal immunoglobulin, albumin) or to kidney function (creatinine). beta 2-microglobulin (beta 2-M), C-RP, lactic dehydrogenase (LDH), and calcemia were also assessed. RESULTS: No correlation was found between LI and serum C-RP. LDH was the sole variable significantly correlated to C-RP (P < 0.01). Besides the biologic parameters used for the staging according to the Durie and Salmon classification, beta 2-M, albumin and LI were significantly different between stages (P < 0.0002, < 0.0004, < 0.00001). LDH and C-RP showed no significant difference. Results were similar when patients with and without bone lesions were analyzed separately. Multivariate analysis ranked these variables as follows with respect to prognostic value: beta 2-M, LI, and age. CONCLUSION: Among the variables analyzed, LI is the sole true reflector of cell proliferation. We confirm its diagnostic and prognostic value.

Adult↗
PubMed1993

[Cyclins A and B: redundancy and specificity].

Mitotic cyclins constitute a regulatory subunit of the histone H1 kinase complex. On the basis of primary structure differences, they are divided into two classes, A and B. Both classes are necessary for mitosis to occur. Cyclins A and B differ in the timing of their cellular expression and in their affinity with the various members of the cdk (cyclin-dependent kinases) family. They also have specific functions: cyclin A plays a role in DNA replication, whereas cyclin B are involved in the inhibition of the fusion of early endosomes and in the activation of cdc25 phosphatase. Cyclins A and B can contribute to the development of neoplastic disorders, either directly (inappropriate expression of the cyclin A gene caused by the hepatitis B virus in hepatocellular carcinoma, interactions between cyclin A and factors involved in the regulation of cell division), or indirectly by causing phosphorylation of oncogene products by a cdk.

CDC2 Protein Kinase↗
PubMed1988

DNA, RNA, and protein content in adult acute myeloid leukemia: effects of cytostatic drugs in vivo.

DNA, RNA, and/or protein cellular content were studied by flow cytometry in 52 cases of acute myeloid leukemia before and on day 4 of remission induction treatment. Bone marrow (BM) samples were stained after fixation by acridine orange for DNA and RNA content (37 cases) and by propidium iodide and fluorescein isothiocyanate for DNA and protein content (52 cases). A positive correlation was found between pretreatment protein content and BM blast involvement: the higher the percentage of blasts in BM smears the higher the mean protein content (p less than 0.05). Protein content was higher in monoblastic leukemia (M4 and M5) than in the granulocytic types (M1, M2, M3) (p less than 0.05). S + G2 + M was higher in patients with protein content below 80 arbitrary units than in the subgroup with protein content above this threshold (p less than 0.05). Pretreatment RNA content, estimated by the RNase-sensitive fraction of G1 cells, was significantly higher in undifferentiated and M1 leukemias than in the other cytological groups (p less than 0.0001). This fraction was higher in patients who subsequently achieved complete remission, but it was not related to BM blast involvement or proliferative fraction of cells. During cytostatic treatment the changes in RNA and protein content did not follow a typical pattern. The connections between variations of DNA, RNA, and protein content and prognosis are examined and their possible relation to drug-induced blast cell maturation is discussed.

Acridine Orange↗
PubMed1988

Phenazone pharmacokinetics as an index of hepatic metabolic efficiency.

Phenazone pharmacokinetics as an index of hepatic microsomal enzyme activity was studied in 31 patients with Hodgkin's disease, 11 patients with non-Hodgkin's lymphoma and 52 healthy volunteers. The mean phenazone half-life (t0.5) was significantly shorter in patients with Hodgkin's disease (8.002 +/- 2.775 h) and in patients with non-Hodgkin's lymphoma (8.775 +/- 2.440 h) than in healthy persons (11.351 +/- 3.706 h). In patients with Hodgkin's disease and in patients with non-Hodgkin's lymphoma mean elimination rate constant (Kel) (0.101 +/- 0.050 h-1; 0.086 +/- 0.028 h-1) and mean metabolic clearance rate (MCR) (70.464 +/- 50.347 ml/min; 71.621 +/- 21.448 ml/min) differed statistically significantly from the same parameters in control group, where K was 0.067 +/- 0.021 h-1 and MCR 49.361 +/- 18.167 ml/min. Treatment with antineoplastic drugs inhibited phenazone elimination. No correlations were found between the phenazone pharmacokinetics parameters and routine laboratory tests of liver function. Since many drugs are metabolized by cytochrome P-450, similar to phenazone, it is likely that their elimination in patients with Hodgkin's disease and in patients with non-Hodgkin's lymphoma will be also changed. This should be considered in selection of their dosage.

Adult↗