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D Wołowiec

Publications and source records attributed to D Wołowiec.

At least 19 recordsLinked to original sources
PubMed2004

Efficacy and safety of fludarabine and cyclophosphamide combined therapy in patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL)-Polish multicentre study.

The aim of this study was to investigate the efficacy of a combination of fludarabine (F) and cyclophosphamide (C) in the treatment of patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL). Between November 1999 and December 2001, 63 patients with B-CLL (median age 60 years) received a regimen that consisted of F 25 mg/m2 and C 250 mg/m2, days 1-3, intravenously, every 4 weeks, for a maximum of 6 courses, Response and toxicity were assessed according to current criteria (NCI-WG and WHO). Complete and partial remissions were achieved in 17.5% and 55.6% of patients, respectively; 19% of patients had stable disease and 7.9% of patients showed disease progression. The median follow-up was 16.5 (range 1.5-32) months. The median duration of progression-free survival (PFS) has not been reached among patients treated with FC regimen as second-line therapy. The median PFS was 13 (range 8-26) months in the 19 responding patients treated with FC regimen as third-line therapy. The most frequent side-effects were neutropenia (45%), thrombocytopenia (42%) and infections (57%). We conclude that the combination of fludarabine and cyclophosphamide demonstrated significant efficacy in pretreated, advanced B-CLL patients, with tolerable toxicity.

Adult↗
PubMed2001

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia.

The objective of the study was to determine the effectiveness and the toxicity of a combined chemotherapy consisting of cladribine (2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of previously untreated B cell chronic lymphocytic leukemia (B-CLL). From August 1998 to December 2000 2-CdA was administered at a dosage of 0.12 mg/kg for 3 (CMC3) or 5 (CMC5) consecutive days, mitoxantrone at 10 mg/m2 on day 1 and cyclophosphamide at 650 mg/m2 on day 1 to 62 patients with advanced or progressive B-CLL. The cycles were repeated at 4 week intervals or longer if severe myelosuppression occurred. Twenty patients received CMC5 and 42 patients CMC3. Within the analyzed group an overall response (OR) rate (CR+PR) of 64.5% (95% CI: 52.7-76.3%) was reported, including 29.0% CR. There was no difference in the CR rate between the patients treated with CMC5 (30%) and CMC3 (28.6%) (P = 0.9), nor in the OR rate (55.0% and 69.0%, respectively, P = 0.3). Residual disease was identified in seven out of 18 (38.9%) patients who were in CR, including two treated with CMC5 and five treated with CMC3 protocols. CMC-induced grade III or IV thrombocytopenia occurred in 12 (19.4%) of patients, including four (20%) CMC5-treated and eight (19%) CMC3-treated patients (P= 0.8). Neutropenia grade III or IV was observed in seven (35%) and 11 (26.2%) patients, respectively (P = 0.8). Severe infections, including pneumonia and sepsis, occurred more frequently after CMC5 (11 patients, 55.0%) than CMC3 (10 patients, 28.6%) (P = 0.03) Fourteen patients died, including six treated with CMC5 and eight treated with CMC3 (30% and 19%, respectively). Infections were the cause of death in nine patients, including four in the CMC5 group and five in the CMC3 group. In conclusion, our results indicate that the CMC programme is an active combined regimen in previously untreated B-CLL patients; its efficiency seems to be similar to that observed earlier in B-CLL patients treated with 2-CdA as a single agent. However, toxicity, especially after CMC5 administration, is significant. Therefore, we recommend the CMC3 but not the CMC5 programme for further evaluation.

Adult↗
PubMed1998

[Hematological problems in patients with bronchial cancer].

Four patients with lung cancer and hematological disorders occurring in different stages of the disease are presented. In three out of them cancer metastases were found prior to the discovery of the primary focus. In two patients those metastases were localized in the bone marrow resulting in the hematological picture of the myelodysplastic syndrome and osteomyelofibrosis. In one of them acute lymphoblastic leukemia developed after short-lasting remission involving the regression of bone marrow metastases of the cancer. In one patient lymph node enlargement, constitutional symptoms and laboratory signs of inflammation led to the preliminary diagnosis of Hodgkin disease. In the remaining patient acute leukemia resistant to chemotherapy developed 34 month after the diagnosis of lung cancer. Our observations point to the necessity of the through diagnosis in every case of hematologic abnormalities of unknown origin and the search of a possible underlying malignancy.

Adult↗
PubMed1996

Differential expression of cell proliferation regulatory proteins in B- and T-lineage acute lymphoblastic leukaemias.

In order to better understand the molecular background of differences between the clinical picture of T- and B-lineage ALLs, we studied the expression of several proteins involved in the regulation of cell proliferation in bone marrow blast cells from 30 cases of previously untreated acute lymphoblastic leukaemia (ALL); 14 cases were T- and 16 B-cell lineage ALLs. We studied several cyclin-dependent kinases (cdk1, cdk2, cdk4, cdk6) and cyclins (cyclin A, cyclin B1, cyclin D3 and cyclin E). We also studied proliferating cell nuclear antigen (PCNA) and Bcl-2 expression, the latter protein known to be involved in the prolonged survival of B-lineage ALL blasts. Proteins obtained from cell lysates were resolved on polyacrylamide gel followed by immunodetection and densitometry of specific bands. Expression of cdk1 and PCNA, markers of proliferative activity, was significantly higher in T- than in B-lineage ALL. Cdk6, which was highly correlated to PCNA, was also higher in T-cell ALL. In contrast, B-lineage ALL displayed a higher expression of anti-apoptotic protein Bcl-2. We hypothesize that those particularities may reflect differential roles of cell multiplication and apoptosis in the neoplastic proliferation of B- and T-lineage ALL.

Adult↗
PubMed1995

Cdk1 is a marker of proliferation in human lymphoid cells.

To better understand the relationship between the proliferation of human lymphoid cells and the expression of cdk1, a catalytic subunit of the histone H1 kinase (H1K), we examined its mRNA and protein content in 3 B-cell lines: Ramos, Reh-6 and IARC 963. Cells were elutriated according to their position in the cell cycle. Cell fractions were analyzed for cdk1 mRNA and protein cellular content by Northern blot and immunoblot, respectively, as well as for H1K activity. Both mRNA and protein amounts and H1K activity varied according to cell cycle phase, the lowest values being observed in G1-enriched fractions. For comparison, elutriated fractions were also tested for the expression of cdk2 and cdk4 proteins. Both showed some variations among fractions, but they were less clear than those of cdk1. We also tested 29 samples of lymphoid neoplastic and non-neoplastic tissues for proliferative activity (percentage of S and G2/M cells estimated by flow cytometry) and expression of cdk1, cdk2 and cdk4 proteins. We found a significant correlation between the percentage of cells in S or S + G2/M phases and cdk1 protein content but not cdk2 or cdk4 content. We conclude that cdk1 expression in human lymphoid cells varies during the cell cycle at both mRNA and protein levels.

Biomarkers↗
PubMed1995

Expression of cell cycle regulatory proteins in chronic lymphocytic leukemias. Comparison with non-Hodgkin's lymphomas and non-neoplastic lymphoid tissue.

The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peripheral blood lymphocytes (PBL) from 25 cases of chronic lymphocytic leukemias (CLL) in order to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison, we also studied the expression of these proteins in: 23 samples of non-Hodgkin's lymphoma (NHL) tissue of different histological types, 10 samples of non-neoplastic lymphoid tissue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated PBL (PHA-PBL) from three healthy donors. Samples were lysed and proteins were resolved on polyacrylamide gel followed by Western blot. The expression of cdk4 and cyclin E, both known to act in early cell cycle stage, was approximately on the same level in all groups of lymphoid pathology examined. In particular, we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk4 positive, ie they expressed these markers over twice the level of non-stimulated healthy PBL. The cdk1 expression was above the level seen in NS-PBL in 14 (56%) cases, but the average expression was significantly lower than in the other tissues examined, including low-grade lymphomas. Cdk2 expression was comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL and in NLT. Cyclins A and B, normally observed in advanced cell cycle phases, were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some cases, indicate that the CLL cells are not quiescent, but are blocked in an early stage of the G1 cell cycle phase, and/or that the expression of these proteins is pathologically deregulated.

Adult↗
PubMed1995

[Cyclin dependent kinases. From molecular biology to pathology].

Cyclin-dependent kinases (cdks) is a family of serine-threonine kinases whose principal role is the promotion of the cell transition through the regulatory points of the cell cycle (G1 and G2/M). The best known human cdks are: cdk1-cdk7 and p58-GTA. The latter one, contrarily to the other cdks, is supposed to act as a antiproliferative factor. Most cdks may be involved in the development of neoplastic disorders. This hypothesis is based on their biological features (interactions with viral oncoproteins), their hyperexpression in some malignancies and frequent deletions of cdk inhibitory genes in cancer cells. cdk5, which displays the maximal kinase activity in non-proliferating brain neurons may participate in the pathogeny of the Alzheimer's disease.

Alzheimer Disease↗
PubMed1994

[Cyclins and proliferative pathology].

Cyclins are proteins which activate a family of serine-threonine kinases called cdk (cyclin-dependent kinases) responsible for progression through the cell cycle. Human cyclins are divided into two groups: mitotic cyclins (cyclins A and B) which regulate cell division, and G1 cyclins (C, D and E) involved in early stages of cell cycle. Cyclins and their cdk partners participate in the pathogenesis of neoplastic proliferation by phosphorylating some oncogenes and antioncogenes, for example the protein encoded by the retinoblastoma susceptibility gene (pRb). Moreover, hyperexpression of one or more classes of cyclins on the gene, mRNA and/or protein level is sometimes observed in neoplastic cells of different origin, for example the rearrangement of the cyclin D1 gene with ectopic expression of its protein product in centrocytic lymphomas with translocation t(11; 14) (q13; q32). Mitotic cyclins can serve as a marker of proliferating cells.

Animals↗
PubMed1993

[Mitotic cyclins--new possibilities for examining mechanisms of neoplasm growth].

Mitotic cyclins constitute a regulatory subunit of the histone H1 kinase complex. On the ground of their primary structure they are divided into two classes A and B, both necessary for the mitosis. Cyclin A activates histone H1 kinase and becomes destroyed by proteolysis earlier than cyclines B and plays an important role in the DNA replication. Cyclins A and B may be involved in the development of neoplastic disorders either directly (inappropriate expression of the cyclin A gene caused by hepatitis B virus in hepatocellular carcinoma, or interactions of this cyclin with factors participating in the regulation of cell proliferation) or indirectly by phosphorylation of some oncogene or antioncogene proteins by a cdk (cyclin dependent kinase).

Animals↗
PubMed1993

[Results of alternating treatment of multiple myeloma--cytostatics VBMCP and recombinant interferon alfa-2B].

In 19 patients with recently diagnosed multiple myeloma 3-week cycles of vincristine, BCNU, melphalan, cyclophosphamide and prednisone alternating with interferon were administered over 6-12 months. Results were compared with a control group of 33 myeloma patients treated exclusively with VBMCP cytostatics. In interferon treated patients objective response was more frequent (76%) and median survival time longer (above 35 months).

Adult↗
PubMed1992

[Early results of the treatment of Hodgkin's disease in adults using the seven-drug cytostatic protocol].

65 adult patients with Hodgkin's disease were treated acc. to multidrug protocol proposed by I. Koza et al. including doxorubicin, vincristine, vinblastine, bleomycin, procarbazine, lomustine and prednisone. 4 drugs (3 cytostatics and prednisone) including cycles were given repeatedly every 4 weeks. In the group of first line therapy (39 persons) 61.5% CR and 23% PR was obtained i.e. 84.5% therapeutic responses. The protocol used as salvage therapy resulted in 30% CR and 23% PR. Undesirable gastrointestinal effects were observed less commonly than after ABVD and CVPP schemes but myelosuppressive effect was more often seen and required attenuation of cytostatic drugs doses in the further cycles of therapy. The considered protocol seems to be a valuable one approaching to -but not achieving- the results of MOPP and ABVD schemes: is better tolerated because of elimination of strong emetic cytostatics (chlormethine and decarbazine) but late toxicity could be evaluable only after several years.

Adolescent↗
PubMed1991

[Correlations between total protein level in the cell and its proliferative activity--an important biological and clinical problem].

The development of investigations method making possible evaluation of the intracellular protein content in the cytoplasm and the occurrence of successive phases of cell division, in particular DNA replication and mitosis. After exposure of the cell to certain chemical or biological factors, e.g. cytostatic drugs, DNA replication and mitosis and the biosynthesis of cytoplasmic macroparticles may be dissociated. Determination of the values of the fractions with low protein content in the cell population in acute leukaemia, that is the percent of cells with cytoplasmic protein below the values observed in phase S, may be clinically important as a prognostic factor in this group of diseases.

Cell Division↗
PubMed1989

[Results of the treatment of non-Hodgkin's lymphoma with 6 cytostatic drug combination].

In 20 patients with non-Hodgkin lymphoma as the first treatment and in 10 patients with the same diagnosis as the second treatment (group II) has been applied the therapeutical protocol proposed by I. Koza et al., composed of 4 monthly cycles of cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone and in the other 4 cycles of doxorubicin, vincristine bleomycin, prednisone. The diagnosis in the I group was: immunoblastic lymphoma in 13 cases, other high grade lymphomas in 5 and low grade lymphoma in 2 cases. In the group II half of the patients showed low or intermediate grade lymphoma but with maximal clinical advancement and resistance to previous therapy. Complete remission (CR) has been obtained in 12 patients of the I group, partial remission (PR) in 7, 1 patient did not respond to therapy. In 3 cases relapse of the disease has been noted, including 2 patients in whom relapse occurred before finishing therapy: the patients remained resistant to alternative one. In the group II the PR and CR has been obtained in 5 and 3 cases respectively: 2 patients with immunoblastic lymphoma resistant to previous therapy did not respond either. Among undesirable effects myelosuppression, mainly granulocytopenia has been mostly noted: infection and septic shock was a cause of death in 1 patient. In 2 patients severe polyneuropathy and in 2 other mucositis of the digestive tract was noted. The treatment used gives beneficial results as induction therapy in cases of immunoblastic lymphoma and enables obtaining remission in therapy resistant cases of low grade lymphoma.

Adolescent↗
PubMedDate not supplied

[Neoplastic diseases of the hematopoietic system and ischemia of the lower limbs].

The possible interaction between hematopoietic neoplasms and ischemia of the lower limbs in patients with both pathologies was subjected to analysis. Anaemia, polycythemia, thrombocythemia, increased leucocytosis in the peripheral blood, and hyperuricemia exerted unfavourable effect on the blood flow through the arteries of the lower limbs. In some cases effective cytostatic treatment diminished the ischemia of the lower limbs. Interactions between various drugs used in the chronic treatment of both pathologies in the same patient was also examined.

Aged↗