Wyniki wyszukiwania

1

Viruses as hijackers of PML nuclear bodies

100%

Moller A., Schmitz M. L.

Archivum Immunologiae et Therapiae Experimentalis

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2003

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tom 51

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nr 5

2

Doxorubicin-transferrin conjugate selectively overcomes multidrug resistance in leukaemia cells

72%

Lubgan D., Jozwiak Z., Grabenbauer G. G., Distel L. V. R.

Cellular and Molecular Biology Letters

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2009

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tom 14

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nr 1

113-127

Neoplastic cells frequently have an increased number of transferrin receptors. Coupling transferrin to an anti-neoplastic drug has the potential to overcome multidrug resistance (MDR). The purpose of this study was to examine the distribution and action of doxorubicin-transferrin conjugate (DOXTRF) in a leukaemia cell line (HL60), a multidrug-resistant leukaemia cell line (HL60ADR) and a normal tissue cell line (human fibroblasts). The intracellular accumulation of DOX and DOX-TRF was monitored by direct fluorescence. More DOX-TRF than free DOX was delivered to the tumour cells, and consecutively the levels of DNA double-strand breaks and apoptosis increased even in the multidrug-resistant cell line. In the normal tissue cell line, DOX-TRF did not accumulate, and therefore, the levels of DNA double-strand breaks and apoptosis did not increase. Cell viability was determined using the MTT assay. The IC50 for DOX-TRF was lower than the IC50 value for the free drug in both leukaemia cell lines. The IC50 values for the HL60 cells were 0.08 μM for DOX and 0.02 μM for DOX-TRF. The IC50 values for HL60ADR cells were 7 μM for DOX and 0.035 μM for DOX-TRF. In conclusion, DOX-TRF was able to overcome MDR in the leukaemia cell lines while having only a very limited effect on normal tissue cells.

3

PML shuttles between nuclear bodies and the cytoplasm

72%

Stuurman N., Floore A., Middelkoop E., Van Driel R., De Jong L.

Cellular and Molecular Biology Letters

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1997

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tom 02

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nr 2

Nuclear bodies are electron dense, spherical structures with a diameter between 0.2 and 1.0 µm. The function of these nuclear domains is unclear. One class of nuclear bodies contains the tumor suppressor protein PML. Besides in the nucleus, a small number of PML-containing structures of about the same size as nuclear bodies is also present in the cytoplasm. We have investigated whether PML is transported from the nucleus to the cytoplasm and/or vice versa. To this end we injected the PML-specific mAb 5E10 into the cytoplasm of living cells. Subsequently, we monitored translocation of the antibody across the nuclear envelope by indirect immunofluorescent microscopy. It is well known that antibodies in the cytoplasm of living cells do not enter the nucleus, unless as a complex with a karyophilic protein. We observed accumulation into PML-containing nuclear bodies of 5E10 microinjected into the cytoplasm. Control rabbit IgG and a mAb specific for lamin B2 were not translocated to the nucleus. All nuclear PML bodies were labeled simultaneously by 5E10 with gradually increased intensity in time. Labeling of PML-containing nuclear bodies by 5E10 microinjected into the cytoplasm was not affected by inhibition of protein synthesis. These results suggest that the 5E10 antigen PML shuttles between the nucleus and cytoplasm, indicating that nuclear bodies are dynamic structures.

4

Molecular diagnostics of promyelocytic leukaemia

72%

Kocki J., Constantinou M., Cioch M., Lancut M., Kaluzewski B., Dmoszynska A., Wojcierowski J.

Journal of Applied Genetics

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2003

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tom 44

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nr 4

5

The GTPase domain of Galphao contributes to the functional interactions of Galphao with the promyelocytic leukemia zinc finger protein

58%

Won J. H., Ghil S. H.

Cellular and Molecular Biology Letters

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2009

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tom 14

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nr 1

46-56

Go, one of the most abundant heterotrimeric G proteins in the brain, is classified as a member of the Gi/Go family based on its homology to Gi proteins. Recently, we identified promyelocytic leukemia zinc finger protein (PLZF) as a candidate downstream effector for the alpha subunit of Go (Gαo). Activated Gαo interacts with PLZF and augments its function as a repressor of transcription and cell growth. G protein-coupled receptor-mediated Gαo activation also enhanced PLZF function. In this study, we determined that the GTPase domain of Gαo contributes to Gαo:PLZF interaction. We also showed that the Gαo GTPase domain is important in modulating the function of PLZF. This data indicates that the GTPase domain of Gαo may be necessary for the functional interaction of Gαo with PLZF.

6

In vitro response of human pathological hematopoietic cells to cladribine

58%

Mazur L., Opydo-Chanek M., Stojak M., Janota B., Blicharski K., Wojcieszek K., Klaput U., Borowicz P.

Folia Biologica

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2013

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tom 61

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nr 3-4

7

In vitro effects of new generation oxazaphosphorines on human promyelocytic leukemia cells

58%

Mazur L., Opydo-Chanek M., Stojak M., Niemeyer U.

Folia Biologica

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2013

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tom 61

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nr 1-2

8

Antileukemic activity of combined epigenetic agents, DNMT inhibitors zebularine and RG108 with HDAC inhibitors, against promyelocytic leukemia HL-60 cells

58%

Savickiene J., Treigyte G., Borutinskaite V.-V., Navakauskiene R.

Cellular and Molecular Biology Letters

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2012

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tom 17

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nr 4

DNMT inhibitors are promising new drugs for cancer therapies. In this study, we have observed the antileukemic action of two diverse DNMT inhibitors, the nucleoside agent zebularine and the non-nucleoside agent RG108, in human promyelocytic leukemia (PML) HL-60 cells. Zebularine but not RG108 caused dose- and time-dependent cell growth inhibition and induction of apoptosis. However, co-treatment with either drug at a non-toxic dose and all trans retinoic acid (RA) reinforced differentiation to granulocytes, while 24 or 48 h-pretreatment with zebularine or RG108 followed by RA alone or in the presence of HDAC inhibitors (sodium phenyl butyrate or BML-210) significantly accelerated and enhanced cell maturation to granulocytes. This occurs in parallel with the expression of a surface biomarker, CD11b, and early changes in histone H4 acetylation and histone H3K4me3 methylation. The application of both drugs to HL-60 cells in continuous or sequential fashion decreased DNMT1 expression, and induced E-cadherin promoter demethylation and reactivation at both the mRNA and the protein levels in association with the induction of granulocytic differentiation. The results confirmed the utility of zebularine and RG108 in combinations with RA and HDAC inhibitors to reinforce differentiation effects in promyelocytic leukemia.

9

Side-chain modified vitamin D analogs require activation of both PI 3-K and erk1,2 signal transduction pathways to induce differentiation of human promyelocytic leukemia cells

58%

Marcinkowska E., Kutner A.

Acta Biochimica Polonica

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2002

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tom 49

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nr 2

Synthetic analogs of vitamin D for potential use in differentiation therapy should selectively regulate genes necessary for differentiation without inducing any perturbations in calcium homeostasis. PRI-1906, an analog of vitamin D2, and PRI-2191, an analog of vitamin D3 bind nuclear vitamin D receptor (nVDR) with substantially lower affinity than 1,25-dihydroxyvitamin D3 (1,25-D3), but have higher differentiation-inducing activity as estimated in HL-60 leukemia cell model. To examine how their increased differentiation-inducing activity is regulated we tested the hypothesis that membrane-mediated events, unrelated to nVDR, take part in the differentiation in response to PRI-1906 and PRI-2191. The induction of leukemia cell differentiation in response to the analogs of vitamin D was inhibited by LY294002 (phosphatidyl- inositol 3-kinase inhibitor), PD98059 (inhibitor of MEK1,2, an upstream regulator of extracellular-signal regulated kinase) and rapamycin (p70 S6K inhibitor) pointing out that activation of signal transduction pathways unrelated to nVDR is necessary for differentiation. On the other hand, inhibition of cytosolic phospholipase A2 accelerated the differentiation of HL-60 cells induced by either 1,25-D3 or by the vitamin D analogs suggesting possible existence of a feedback loop between extracellular-signal regulated kinases and phospholipase A2.

Ograniczanie wyników

Viruses as hijackers of PML nuclear bodies

Doxorubicin-transferrin conjugate selectively overcomes multidrug resistance in leukaemia cells

PML shuttles between nuclear bodies and the cytoplasm

Molecular diagnostics of promyelocytic leukaemia

The GTPase domain of Galphao contributes to the functional interactions of Galphao with the promyelocytic leukemia zinc finger protein

In vitro response of human pathological hematopoietic cells to cladribine

In vitro effects of new generation oxazaphosphorines on human promyelocytic leukemia cells

Antileukemic activity of combined epigenetic agents, DNMT inhibitors zebularine and RG108 with HDAC inhibitors, against promyelocytic leukemia HL-60 cells

Side-chain modified vitamin D analogs require activation of both PI 3-K and erk1,2 signal transduction pathways to induce differentiation of human promyelocytic leukemia cells