Search results

1

Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia coli L-asparaginase.

100%

Kozak M., Jaskólski M., Röhm K. H.

Acta Biochimica Polonica

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2000

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vol. 47

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issue 3

807-814

EN

Periplasmic Escherichia coli L-asparaginase II with Y25F mutation in the active-site cavity has been obtained by recombinant techniques. The protein was crystallized in a new hexagonal form (P6522). Single crystals of this polymorph, suitable for X-ray diffraction, were obtained by vapor diffusion using 2-methyl-2,4-pentanediol as precipitant (pH 4.8). The crystals are characterized by a = 81.0, c = 341.1 Å and diffract to 2.45 Å resolution. The asymmetric unit contains two protein molecules arranged into an AB dimer. The physiologically relevant ABA'B' homotetramer is generated by the action of the crystallographic 2-fold axis along [1, -1, 0]. Kinetic studies show that the loss of the phenolic hydroxyl group at position 25 brought about by the replacement of Y with F strongly impairs kcat without significantly affecting Km.

2

Cytotoxic effect of nitric oxide on human hematological malignant cells.

100%

Tsumori M., Tanaka J., Koshimura K., Kawaguchi M., Murakami Y., Kato Y.

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vol. 49

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issue 1

139-144

EN

We investigated the cytotoxic effect of nitric oxide (NO) on primary culture of human hematological malignant cells. Sodium nitroprusside (SNP), an NO donor, had cytotoxic effects on the cells of some patients with malignant lymphoma (ML), acute myelocytic leukemia (AML) or chronic myelomonocytic leukemia (CMMoL), but not with multiple myeloma. Cultured cells from the ML patient remained sensitive to SNP after the cells became resistant to anti-cancer drugs. In contrast, the cells from the patients with AML and CMMoL became resistant to SNP while anti-cancer drugs remained effective. In samples of the cells of the patients with ML and AML, the number of CD3 positive lymphoma cell was decreased by SNP and the number of CD33 negative cells and normal B lymphocytes (CD19 positive cells) were increased. In the cells of the patient with ML, apoptosis was induced by SNP. SNP had no effect on lymphocytes of healthy volunteers. These results suggest that SNP had an anti-tumor effect on human hematological malignant cells.

3

Influence of BCR/ABL fusion proteins on the course of Ph leukemias.

100%

Telegeev G. D., Dubrovska A. N., Dybkov M. V., Maliuta S. S.

Acta Biochimica Polonica

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2004

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vol. 51

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issue 3

845-849

EN

The hallmark of chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) is the presence of the Philadelphia chromosome as a result of the t(9;22) translocation. This gene rearrangement results in the production of a novel oncoprotein, BCR/ABL, a constitutively active tyrosine kinase. There is compelling evidence that the malignant transformation by BCR/ABL is critically dependent on its Abl tyrosine kinase activity. Also the bcr part of the hybrid gene takes part in realization of the malignant phenotype. We supposed that additional mutations accumulate in this region of the BCR/ABL oncogene during the development of the malignant blast crisis in CML patients. In ALL patients having p210 fusion protein the mutations were supposed to be preexisting. Sequencing of PCR product of the BCR/ABL gene (Dbl, PH region) showed that along with single-nucleotide substitutions other mutations, mostly deletions, had occurred. In an ALL patient a deletion of the 5th exon was detected. The size of the deletions varied from 36 to 220 amino acids. For one case of blast crisis of CML changes in the character of actin organization were observed. Taking into account the functional role of these domains in the cell an etiological role of such mutations on the disease phenotype and leukemia progression is plausible.

4

In vitro activity of oxazaphosphorines in childhood acute leukemia: Preliminary report.

88%

Styczyński J., Wysocki M., Dębski R., Balwierz W., Rokicka-Milewska R., Matysiak M., Balcerska A., Kowalczyk J., Wachowiak J., Sońta-Jakimczyk D., Chybicka A.

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vol. 49

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issue 1

221-225

EN

Glufosfamide (β-D-glucosyl-ifosfamide mustard) is a new agent for cancer chemotherapy. Its pharmacology is similar to commonly used oxazaphosphorines, but it does not require activation by hepatic cytochrome P-450 and preclinically demonstrates lower nephrotoxicity and myelosuppression than ifosfamide. The aim of the study was a comparison of the drug resistance profiles of glufosfamide and other oxazaphosphorines in childhood acute leukemias. Leukemic cells, taken from children with ALL on diagnosis (n = 41), ALL on relapse (n = 12) and AML on diagnosis (n= 13) were analyzed by means of the MTT assay. The following drugs were tested: glufosfamide (GLU), 4-HOO-ifosfamide (IFO), 4-HOO-cyclophosphamide (CYC) and mafosfamide cyclohexylamine salt (MAF). In the group of initial ALL samples median cytotoxicity values for GLU, IFO, CYC and MAF were 15.5, 33.8, 15.7 and 7.8 μM, respectively. In comparison with initial ALL samples, the relative resistance for GLU and IFO in relapsed ALL samples was 1.9 (p = 0.049) and 1.3 (ns), and in initial AML samples 31 (p < 0.001) and 5 (p = 0.001), respectively. All oxazaphosphorines presented highly significant cross-resistance. Glufosfamide presented high activity against lymphoblasts both on diagnosis and on relapse.

5

Monocytes in children with leukemias and lymphomas - down-regulation of HLA and costimulatory molecules.

88%

Łuczyński W., Stasiak-Barmuta A., Krawczuk-Rybak M., Szymański M., Malinowska I., Mitura-Lesiuk M.

Acta Biochimica Polonica

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2004

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vol. 51

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issue 4

1067-1073

EN

The aim of the study was to evaluate the function of monocytes in children with leukemias and lymphomas based on the expression of critical costimulatory, activatory and adhesion molecules (CD80, CD86, HLA-DR and CD54 = ICAM-1), estimated with tricolor flow cytometry. In comparison to the control group we found a lower percentage of monocytes with costimulatory molecules (CD80 before and CD86 after lipopolysaccharide stimulation) at the time of diagnosis and of monocytes with HLA-DR molecules after remission induction. We also noted a lower percentage of monocytes with HLA-DR expression in the group with severe or therapy resistant infections. The results of our investigation suggest some defect in costimulation and antigen presentation in lymphoproliferative diseases in children.

6

Outcomes of Jehovah’s Witnesses with hematological malignancies treated without transfusions — single center experience

75%

Drozd-Sokołowska J. E., Waszczuk-Gajda A., Dwilewicz-Trojaczek J., Walesiak A., Krzyżanowska M., Paluszewska M., Wieczorek J., Wiktor-Jędrzejczak W., Drozd-Sokołowska J. E., Waszczuk-Gajda A., Dwilewicz-Trojaczek J., Walesiak A., Krzyżanowska M., Paluszewska M., Wieczorek J., Wiktor-Jędrzejczak W.

Folia Medica Cracoviensia

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2020

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vol. 60

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issue 4

7

Cytotoxic effects of cladribine and tezacitabine toward HL-60.

75%

Stachnik K., Grieb P., Skierski J. S.

Acta Biochimica Polonica

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2005

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vol. 52

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issue 2

561-565

EN

The aim of the study was to determine the relation between the cytotoxic and cytostatic effects of tezacitabine and cladribine on a HL-60 cell line and the time of exposure of cells to these drugs. Cell viability and induction of apoptosis were assessed using flow cytometry methods. Apoptosis was confirmed by direct microscopic observation. Growth inhibition was examined by cell counting. After 24 h incubation tezacitabine was equally or less toxic compared to cladribine. However, toxicity of tezacitabine strongly rose after 48 h incubation leading to massive cell death at doses much lower than those of cladribine. Assessment of the effect of increased exposure time on the clinical efficacy of tezacitabine is indicated.

8

Chemioterapia w ciąży

63%

Sznurkowski J. J., Klasa-Mazurkiewicz D., Kobierski J., Wydra D., Emerich J.

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EN

Chemotherapy in the treatment of malignant tumors in pregnant women potentially threatens life and development of the fetus. Aim of paper: The purpose of this paper was to update current knowledge concerning the role of chemotherapy in combination therapy of gynecologic malignancies complicating pregnancy and to review available literature focusing on potential sequels of administration of chemotherapeutics at different time-points in pregnancy, with particular emphasis on fetal development, course of pregnancy and future lot of the child. Method: The PubMed database was searched using the following key words: methotrexate; 5-fluorouracil; aminopterin; thioguanine; mercaptopurine; cyclophosphamide; busulfan; ifosfamide; chlorambucil; dacarbazine; doxorubicin; daunorubicin; adriamycin; idarubicin; epirubicin; dactinomycin; bleomycin; mitoxantrone; vincristine; vinblastine; vinorelbine; paclitaxel; docetaxel; cisplatin; carboplatin; prednisone; tamoxifen; etoposide; teniposide; allopurinol; malformation; IUGR; chemotherapy; pregnancy. Search criteria were fulfilled by 33 papers (selected chemotherapeutic agent/pregnancy/malformation), which subsequently underwent content-related analysis. Conclusions: A decision on the use of chemotherapy during pregnancy should be made depending on type and stage of malignancy. It at all possible, administration of cytostatics should be delayed until the end of first trimester. If the patient requires multidrug therapy in the first trimester, she should receive anthracycline-derived antibiotics combined with Vinca alkaloids or should be placed on monotherapy and after 12 weeks shift to a multidrug regimen. Delivery should be planned for the 35th gestational week and 2-3 weeks after termination of chemotherapy in order to allow recovery of bone-marrow function.

PL

Chemioterapia w leczeniu nowotworów złośliwych u kobiet w ciąży stanowi potencjalne zagrożenie dla życia i rozwoju płodu. Celem pracy było przybliżenie wiedzy na temat udziału chemioterapii w leczeniu skojarzonym nowotworów ginekologicznych wikłających ciążę oraz dokonanie przeglądu doniesień medycznych pod kątem skutków zastosowania poszczególnych czynników chemioterapeutycznych w różnych trymestrach ciąży, ze szczególnym uwzględnieniem wpływu na rozwój płodu, przebieg ciąży i dalsze losy dziecka. Metoda: Przy użyciu słów kluczowych: methotrexate; 5-fluorouracil; aminopterin; thioguanine; mercaptopurine; cyclophosphamide; busulfan; ifosfamide; chlorambucil; dacarbazine; doxorubicin; daunorubicin; adriamycin; idarubicin; epirubicin; dactinomycin; bleomycin; mitoxantrone; vincristine; vinblastine; vinorelbine; paclitaxel; docetaxel; cisplatin; carboplatin; prednisone; tamoxifen; etoposide; teniposide; allopurinol; malformation; IUGR; chemotherapy; pregnancy przeszukano bazę PubMed. Odnaleziono 33 artykuły anglojęzyczne spełniające kryteria wyszukiwania (wybrany czynnik chemioterapeutyczny/ciąża/malformacja), które poddano analizie merytorycznej. Wnioski: Decyzję o chemioterapii w ciąży należy podjąć stosownie do rodzaju nowotworu i jego stopnia zaawansowania klinicznego. Jeśli jest to tylko możliwe, należy odroczyć podawanie cytostatyków do końca pierwszego trymestru. W sytuacji, w której pacjentka wymaga terapii wielolekowej w pierwszym trymestrze, należy rozważyć zastosowanie antybiotyków antracyklinowych w połączeniu z alkaloidami Vinca lub rozpocząć leczenie terapią jednolekową i po 12 tygodniach przejść na schemat wielolekowy. Poród powinien być zaplanowany na 2 do 3 tygodni po zakończeniu chemioterapii, w celu umożliwienia powrotu prawidłowej czynności szpiku (około 35. tygodnia).

Refine search results

Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia coli L-asparaginase.

Cytotoxic effect of nitric oxide on human hematological malignant cells.

Influence of BCR/ABL fusion proteins on the course of Ph leukemias.

In vitro activity of oxazaphosphorines in childhood acute leukemia: Preliminary report.

Monocytes in children with leukemias and lymphomas - down-regulation of HLA and costimulatory molecules.

Outcomes of Jehovah’s Witnesses with hematological malignancies treated without transfusions — single center experience

Cytotoxic effects of cladribine and tezacitabine toward HL-60.

Chemioterapia w ciąży