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Biomedical subjects

G Mazur

Publications and source records attributed to G Mazur.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR-ABL--positive acute lymphoblastic leukemia-retrospective analysis of Polish Adult Leukemia Group (PALG).

Patients with Philadelphia chromosome-positive (Ph+) and/or BCR-ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR-ABL+ ALL registered in Poland in 1997-2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR-ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed.

Adolescent↗
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↗
PubMed2006

Lack of association between the TNF-alpha promoter gene polymorphism and susceptibility to B-cell chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (B-CLL) is a lymphoproliferative disorder characterized by clonal expansion of B lymphocytes. The present study aimed to determine whether there is an association between the polymorphic features located within the promoter/enhancer region of tumour necrosis factor-alpha (TNFA) gene and susceptibility to B-CLL. TNFA (-308 G/A) promoter single nucleotide polymorphism (SNP) was determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) using commercial oligonucleotides. No significant association was found between the distribution of TNFA alleles and B-CLL in Polish patients with B-CLL. Our single centre results were compared with other literature data and combined in a cumulative analysis employing the Mantel-Haenszel method. Among 183 B-CLL patients, 47 (26%) were carrying TNFA*2 allele and this allele was present in 98 out of 348 controls (28%). Also, the results of the Mantel-Haenszel test did not show a significant correlation [Mantel-Haenszel estimate of approximate relative risk (RMH) = 0.86, P = 0.294]. These results suggest that TNFA (-308) alleles are not involved in the predisposition to the development of B-CLL.

Adult↗
PubMed2006

Angiogenic and coagulation-fibrinolysis factors in non Hodgkin's lymphoma.

High serum VEGF and bFGF levels are independent prognostic factors of poor prognosis in NHL patients. There is growing evidence that both angiogenesis and haemostatic aberrancies are integral parts of the pathobiology of cancer growth and dissemination. The purpose of the study was: (a) to analyze relations of VEGF and bFGF serum levels, fibrinogen and D-dimer plasma levels with lymphoma Ann Arbor Staging System (AASS) and International Prognostic Index (IPI) and, (b) to evaluate correlations between serum levels of angiogenic cytokines and plasma levels of coagulation-fibrinolysis factors in 52 previously untreated NHL patients included to the study. The control group consisted of 23 healthy volunteers. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined on Behring Coagulation System (BCS) equipment. In lymphoma group serum VEGF and bFGF levels were significantly higher than in the control. Differences in concentrations of VEGF, bFGF between II, III and IV stage of disease acc. AASS were not statistically significant. Plasma levels of fibrinogen and D-dimer were elevated in lymphoma patients when compared with the control. Fibrinogen plasma levels were similar in all stages. The D-dimer level was significantly higher in patients with IV stage in comparison to stage II and III. Statistically significant differences of VEGF and bFGF serum levels were observed only between intermediate/high and high risk groups acc. IPI. Fibrinogen plasma levels were significantly higher in high risk group than in low risk group. D-dimer plasma levels were significantly higher in high risk group than in low risk group and low/intermediate group. We observed positive correlation between serum level of VEGF and plasma level of fibrinogen, and between serum level of bFGF and plasma level of fibrinogen. There was also negative correlation between serum level of VEGF and plasma level of D-dimer, and between serum level of bFGF and plasma level of D- dimer. Our study indicates that D-dimer level, but not VEGF, bFGF and fibrinogen correlates with AASS and IPI in NHL patients. Significant correlations between levels of VEGF/bFGF and fibrinogen/D-dimer suggest specific interactions between angiogenic and coagulation-fibrinolysis system.

Female↗
PubMed2005

A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group.

Purine nucleoside analogues, cladribine (2-chlorodeoxyadenosine, 2-CdA) and fludarabine (FAMP) are active agents in acute myeloid leukemias (AMLs). Synergistic interaction between FAMP or 2-CdA with cytarabine (cytosine arabinoside, Ara-C) has been demonstrated in preclinical and clinical studies. The current multicenter phase II study was initiated to evaluate the efficacy and toxicity of induction treatment consisting of 2-CdA (5 mg/m2), Ara-C (2 g/m2), mitoxantrone (MIT, 10 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (CLAG-M) in refractory AML. In case of partial remission, a second CLAG-M was administered. Patients in complete remission (CR) received consolidation courses based on high-dose Ara-C and MIT with or without 2-CdA. Forty-three patients from five centers were registered: 25 primary resistant and 18 relapsed. CR was achieved in 21 (49%) patients, 20 (47%) were refractory and 2 (5%) died early. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS; 1 year) for the 42 patients as a whole and the 20 patients in CR were 43% and 73%, respectively. Disease-free survival (1 year) was 68.6%. None of the analyzed prognostic factors influenced the CR and OS probability significantly. We conclude that CLAG-M regimen has significant antileukemia activity in refractory AML, which seems to be better than the activity of many other regimens. The toxicity of the treatment is acceptable.

Acute Disease↗
PubMed2005

Endostatin serum level in acute myeloid leukemia.

Increased levels of tumor angiogenesis have been demonstrated in variety of solid tumors and hematological malignancies including acute myeloid leukemia (AML). The aim of the study was to evaluate serum level of endostatin in newly diagnosed patients with AML before chemotherapy and after achieving complete remission (CR). Serum samples from 68 adult patients (28 females and 40 males, median age 42 years, range 21-83 years) with AML had been taken before chemotherapy was administered. In addition 21 out of 68 patient were analyzed again after achieving CR. Endostatin levels were measured using ChemiKine sandwich ELISA kit (Chemicon International). Twelve samples from healthy volunteers (5 females and 7 males, median age 40 years; range 35-65 years) were evaluated as the control. Endostatin serum levels were significantly higher in untreated AML patients than in the normal controls. In AML patients baseline endostatin levels were significantly lower than in CR. We did not found any correlation between white cell count or percentage of blasts in the bone marrow and endostatin level. Moreover endostatin levels did not differ statistically among AML FAB subgroups. Increased endostatin plasma levels may reflect intensity of inhibition of angiogenesis and may by useful in prognosis of CR in AML. Chemotherapy can modulate the regulation of angiogenesis in AML patients.

Acute Disease↗
PubMed2005

LYVE-1 expression on high endothelial venules (HEVs) of lymph nodes.

LYVE-1 (lymphatic endothelium hyaluronan receptor) has been identified as a powerful marker for lymphatic endothelium. Apart from lymphatic endothelium, LYVE-1 is expressed in normal liver blood sinusoids, spleen endothelium and activated tissue macrophages. LYVE-1 has not been detected in blood vascular endothelium with the exception of blood vessels in the lung. High endothelial venules (HEVs) belong to the vascular compartment of lymph nodes. They are the major site of entry for circulating lymphocytes into the node. HEVs are characterized by cuboidal endothelial cells, the existence of discontinuous junctions between these endothelial cells, and the presence of large numbers of lymphocytes within their walls. 40 paraffin-embedded lymph node biopsy specimens from newly diagnosed patients with non-Hodgkin lymphoma were evaluated as well as 10 lymph node biopsy specimens from adult patients with reactive lymphadenitis, and 10 normal, non-metastatic lymph nodes obtained from adult patients during cancer surgery served as controls. Samples were fixed in 10% buffered formalin, paraffin embedded, and stained with hematoxylin and eosin for histopathological evaluation. Sections were also evaluated with mouse monoclonal antibodies against LYVE-1 and CD34, and expression of both LYVE-1 and CD34 was demonstrated in HEVs. LYVE-1 expression was also found on the endothelial cells of the lymphatic sinus and in reticular cells in the lymph nodes.

Antigens, CD34↗
PubMed2004

Contribution of flow cytometric immunophenotyping and bone marrow trephine biopsy in the detection of lymphoid bone marrow infiltration in non-Hodgkin's lymphomas.

The bone marrow (BM) is a frequent site of involvement in non-Hodgkińs lymphomas (NHL) and evidence of an infiltrated BM may implicate different therapeutical regimens. Flow cytometric immunophenotyping of bone marrow aspirates now is included in the assessment of patients with NHL and used as an adjunct to morphologic evaluation in the staging of lymphoma. The aim of the study was to compare flow cytometric immunophenotyping of BM and paraffin section staining of BM biopsies in the marrow involvement of NHL. Cytometric immunophenotyping of bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in 53 B- and T-cell lymphoma patients were performed. We used the following fluorochrom conjugated monoclonal antibodies specific for: CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, CD22, CD23, CD79B, FMC7 and Ig kappagamma light chain. Unilateral BM trephine biopsies were obtained in all cases, fixed, decalcified and paraffin-embedded. Morphologic marrow involvement by lymphoma was found in 24 cases; flow immunophenotyping identified 26 cases with NHL: morphology-positive/flow-positive (n=21), morphology positive/flow-negative (n=3), morphology-negative/flow-positive (n=4), and morphology-negative/flow-negative (n=23). The concurrence rate of BM trephine biopsy and flow cytometric immunophenotyping in evaluation of NHL bone marrow infiltration was 88.7%. Immunophenotyping of the bone marrow of NHL patients by flow cytometry is helpful for assessment of bone marrow infiltration, especially in B-cell disorders. Both trephine biopsies and flow cytometry are better than single investigation for detection of infiltration in NHL.

Adult↗
PubMed2004

Macrophage/histiocytic antigen CD68 expression in neoplastic and reactive lymph nodes.

There are some reports, suggesting that infiltrating macrophages may promote tumour progression in non-Hodgkin's lymphoma (nHL). The aim of the study was an evaluation of macrophages, marked by antibody against CD68 in indolent and aggressive nHL. The study was performed in 65 patients: 50 with nHL and 15 with lymph nodes affected by reactive hyperplasia. Immunohistochemical analyses were performed on paraffin-embedded specimens with monoclonal anti-CD68 antibody. Scoring on the basis of the percentage of positive cells indicated CD68 expression in 34/50 (68%) of the patients with nHL and in only 5/15 (33%) of the patients with reactive hyperplasia. The expression of CD68 was statistically significantly higher in the aggressive nHL than in indolent nHL. An increased number of CD68 positive macrophages in clinically aggressive nHL may confirm their role in tumour progression.

Antigens, CD↗
PubMed2004

Survivin expression in lymph nodes, affected by lymphoma and reactive hyperplasia.

Survivin is a member of the inhibitors from the apoptosis family over-expressed in various human cancers. The aim of the study was to evaluate the expression of survivin in lymph nodes, invaded by non-Hodgkin's lymphomas (nHL) and in lymph nodes reactive hyperplasia. We analysed paraffin sections obtained from 50 patients with nHL and from 13 patients with reactive hyperplasia using, an anti-survivin antibody. There was abundant immunoreactivity cytoplasm in 34/50 (68%) patients with nHL and in only 5/13 (38%) with reactive hyperplasia. Out of the 27 patients with aggressive nHL, 19 (70%) revealed survivin expression in almost all tumour cells. Out of the 23 patients with indolent nHL, 16 (70%) revealed the expression but with lower immunoreactivity score. The study indicates that patients with nHL presented a high level of survivin expression, it was more pronounced in aggressive than in indolent nHL.

Humans↗
PubMed2003

Acute lymphoblastic leukemia in elderly: the Polish Adult Leukemia Group (PALG) experience.

This is a retrospective, multicenter study to evaluate biological features and outcome of elderly patients diagnosed with acute lymphoblastic leukemia (ALL) during the last 10 years in ten hematological centers in Poland. Eighty-seven patients aged 60 years or older were studied. To our knowledge, this is one of the largest group of elderly patients with ALL evaluated. We have not observed differences in immunological subtypes and Ph chromosome incidence as compared with younger adult ALL presented in the literature. Induction chemotherapy was administered in 75 patients. We observed complete remission (CR) in 34 (45%, 95% CI: 33-56%) patients. Induction death occurred in 11 (15%) patients. Thirty patients (40%) showed primary resistance to chemotherapy. Median overall survival (OS) of all patients was 150 days. Median disease-free survival (DFS) of responding patients was 180 days. We observed four long-term survivors (DFS longer than 3 years) in our group of patients. Factors influencing OS were CR achievement, female gender, and WBC below 30 x 10(9)/l. Male gender was the only prognostic factor negatively affecting probability to achieve CR. We have not observed any differences in either biology or outcome between patients aged 60-69 years and those aged more than 70 years. ALL of the elderly is a rare disease with poor prognosis. Further clinical trials evaluating the disease features, outcome, and new therapeutic approaches are warranted.

Aged↗
PubMed2002

High-dose chemotherapy with autologous stem cell transplantation is an effective treatment of primary refractory Hodgkin's disease. Retrospective study of the Polish Lymphoma Research Group.

We analysed the treatment outcome of primary refractory HD patients managed with high-dose chemotherapy and haematopoietic cell transplantation. Data of 65 adult patients who underwent HDC/ASCT in nine Polish centres for primary resistant Hodgkin's disease between June 1991 and July 2000 were collected retrospectively. Response rate to HDC/ASC: CR, 54%; PR, 20%; less than PR, 15%; early deaths, 11%. Actuarial 3-year OS and PFS were 55% and 36%, respectively. In multivariate analysis, lack of bulky lymph nodes and use of immunotherapy were favourable factors for both OS and PFS. IPF <3 at the time of transplantation was predictive for PFS. However, the prognostic impact of immunotherapy should be interpreted with caution since this group included more patients who achieved CR after HDC/ASCT. The results of HDC/ASCT are encouraging and confirm earlier findings. The role of immunotherapy should be further investigated in prospective trials.

Adolescent↗
PubMed2002

The treatment of acute myeloid leukemia with mitoxantrone, etoposide and low-dose cytarabine in elderly patients - a report of Polish Acute Leukemia Group (PALG) phase II study.

The common dilemma in the treatment of elderly patients with acute myeloid leukemia (AML) is whether to use intensive myelosuppresive therapy with higher risk of treatment related mortality (TRM), but a chance for complete remission (CR), or to treat less intensively in order to prolong survival time with a better quality of life. The aim of this prospective, phase II study was to assess the efficacy and toxicity of low dose combination induction treatment consisted of cytarabine at a dose of 10 mg/m2 every 12 h s.c. for 7 days, VP-16 at a dose of 100 mg/day p.o. for 7 days and mitoxantrone at a dose of 6 mg/m2 i.v daily on days 1-3. Two induction courses were planned. In the group of 44 patients 12 (27%) achieved CR, 4 (9%) patients were in PR and there were 9 (20%) early deaths (ED). Age, performance status, preceding myelodysplastic syndrome, karyotype, WBC and % of blasts in bone marrow were not significant prognostic factors for CR probability. The following initial factors appeared to be related to a shorter duration of survival time from the start of treatment: age >70 (p<0.03), poor performance status (p<0.03), and % of BM blasts 50 (p<0.05). We conclude that, despite promising results in the pilot study the efficacy of this induction treatment is not better than the efficacy of other regimens. The hematological toxicity of this treatment seems to be comparable with "3+7" regimen.

Acute Disease↗
PubMed2001

[Cephalosporins in empirical treatment of neutropenic fever].

Neutropenic fever and infection became a significant clinical problem with the common use of chemotherapy of cancer. The cephalosporins are a large group of beta-lactam antimicrobial agents. Because of their broad spectrum of activity and low toxicity, they are excellent choice for initial empirical treatment of fever in neutropenia. The article summarises the role of third and fourth generation cephalosporins in therapy of neutropenic fever.

Antineoplastic Agents↗
PubMed2000

Transforming growth factor-beta1 is a potent inhibitor of secretory leukoprotease inhibitor expression in a bronchial epithelial cell line. Munich Lung Transplant Group.

Obliterative bronchiolitis (OB) is the major long-term complication following lung and heart-lung transplantation. In bronchoalveolar lavage fluid samples obtained from patients suffering from OB, a marked increase in the number of neutrophils and elevated expression of transforming growth factor (TGF)-beta1 had been found. The goal of the study was to evaluate whether TGF-beta1 is capable of interfering with the expression of the secretory leukoprotease inhibitor (SLPI), the dominating defence of the conducting airways against neutrophil elastase (NE). The authors analysed the effects of TGF-beta1 on gene expression and protein release of SLPI by cultured human bronchial epithelial (BEAS-2B) cells. SLPI protein levels in the supernatants were quantified with a specific enzyme-linked immunosorbent assay; SLPI messenger ribonucleic acid (mRNA) levels were measured by reverse transcriptase polymerase chain reaction. Incubation with TGF-beta1 induced a marked decrease in SLPI protein levels (1 ng x mL(-1) TGF-beta1: stimulation index (SI; protein: relation to SLPI protein release of resting cells)=0.56; 10 ng x mL(-1) TGF-beta1: SI=0.48; 50 ng x mL(-1) TGF-beta1: SI=0.37, p<0.01 each) and mRNA expression (1 ng x mL(-1) TGF-beta1: SI (SI mRNA: relation to SLPI mRNA expression of resting cells)=0.46; 10 ng x mL(-1) TGF-beta1: SI=0.31; 50 ng x mL(-1) TGF-beta1: SI=0.18, p<0.01 each) in a dose dependent fashion. Simultaneous incubation of BEAS-2B cells with TGF-beta1 and NE also caused a significant reduction in SLPI synthesis (10 ng x mL(-1) TGF-beta1 + 7.5 U x mL(-1) NE: mRNA SI=0.61, p<0.05; protein SI=0.65, p<0.05; 50 ng x mL(-1) TGF-beta1 + 7.5 U x mL(-1) NE: mRNASI=0.52, p<0.05; protein SI=0.58, p<0.05; 10 ng x mL(-1) TGF-beta1: mRNA SI=0.33, p<0.01; protein SI=0.38, p<0.01). In conclusion, the data suggest that the coincidence of neutrophilia and upregulation of transforming growth factor-beta1 in obliterative bronchiolitis may lead to uninhibited neutrophil elastase activity by downregulation of secretory leukoprotease inhibitor, with the consequence of ongoing injury to the epithelium.

Bronchi↗
PubMed2000

[Palatine tonsil lymphoma in ENT department in Bełchatów for the of 1987-1998].

The authors present 10 cases of malignant lymphomas of the head and neck hospitalized in ENT Department of Regional Hospital in Belchatów. The two cases of tonsil lymphomas were described in detail calling attention to diagnostic difficulties. The false result of aspiration biopsy caused prolongation of diagnostic procedure.

Adult↗