Biomedical subjects

J Jakubikova

Publications and source records attributed to J Jakubikova.

6 recordsLinked to original sources

PubMed2006

Sensitisation for cisplatin-induced apoptosis by isothiocyanate E-4IB leads to signalling pathways alterations.

A new synthetic isothiocyanate (ITC) derivative, ethyl 4-isothiocyanatobutanoate (E-4IB), appeared to be an effective modulator of cellular proliferation and potent inducer of apoptosis. In cooperation with cisplatin, this compound exerted synergistic effects in human ovarian carcinoma A2780 cells. In the present study we investigated in more detail E4IB-sensitisation for cisplatin-induced apoptosis. Sequential administration of both cytostatic agents led to increased intracellular platinum accumulation, glutathione level depletion and mitochondrial membrane potential dissipation. These events were accompanied with poly (ADP-ribosyl) polymerase cleavage, stimulation of caspase-3 activity, upregulation of p53, FasL and Gadd45alpha, cyclin B1 downregulation and an increase in mitogen-activated protein kinases JNK, ERK and p38 phosphorylation as well as PI3K level alterations. The presented results might have implications for developing new strategies aimed at therapeutic benefit of natural or synthetic ITCs in cooperation with various anticancer drugs.

Antineoplastic Agents↗

PubMed2006

Combine cancer gene therapy harnessing plasmids expressing human tumor necrosis factor alpha and Herpes simplex thymidine kinase suicide gene.

We have assessed the effect of combine cancer gene therapy with exogenous human tumor necrosis factor alpha (hTNFalpha) and suicide gene therapy on three human cancer cell lines MCF-7 (breast adenocarcinoma), U-118MGand 42-MG-BA (human gliomas). Transfection of a plasmid containing hTNFalpha under the control of a hybrid promoter resulted in expression of hTNFalpha gene in vitro. Transduction of retroviral plasmid containing Herpes simplex thymidine kinase (HSVtk) led to the expression of thymidine kinase in all three cell lines. MTT cell proliferation assay and flow cytometric analysis showed a significant increase in apoptotic and necrotic cells and decrease of proliferation in all cell lines after combine therapy with hTNFalpha expression plus thymidine kinase/GCV suicide system. The presence of these two genes after transduction of retroviral vector containing thymidine kinase and hTNFalpha was confirmed by PCR. The expression of HSVtk gene was proved by Western blot analysis, and the expression of both genes was confirmed by RT-PCR. Additive cell killing effect due to presence of HSVtk and hTNFalpha therapeutic genes after activation of non-toxic prodrug was observed. Whether the bicistronic plasmid containing both genes would improve the therapeutic effect need to be assessed in the future.

Antiviral Agents↗

PubMed2006

Isothiocyanate iberin modulates phase II enzymes, posttranslational modification of histones and inhibits growth of Caco-2 cells by inducing apoptosis.

The aim of presented study was to further investigate the concentration-dependent changes induced by isothiocyanate iberin (IBN) in human colon carcinoma Caco-2 cells. The concentrations of IBN below IC(50) value (18 microM, 72 h) triggered the augmentation of mRNA levels for phase II detoxification GSTA1 and UGT1A1 enzymes and antioxidant thioredoxin reductase 1 gene in cells treated for 24 h. In addition a significant increase of acetylated H4 histone was detected. The mRNA induction peaked at IC(50) value and returned to level of control cells at 40 microM concentration of IBN. The cell cycle changes, gamma-H2AX stainability and the increase of phospho-H3 mitotic marker were induced at concentrations above IC(50) value. Appearance of Annexin V positive apoptotic cells and sub-G1 fragmented DNA as well as decrease of mitochondrial transmembrane potential confirmed cytotoxic effect of IBN observed in MTT assay. The predominance of necrotic cells and profound positivity of gamma-H2AX took place at the highest concentration of IBN. Thus, IBN represents the effective member of natural chemopreventive isothiocyanate family with which apoptotic potential can by employed to eliminate tumor cells.

Acetylation↗

PubMed2002

PK11195, an isoquinoline carboxamide ligand of the mitochondrial benzodiazepine receptor, increased drug uptake and facilitated drug-induced apoptosis in human multidrug-resistant leukemia cells in vitro.

The isoquinoline peripheral benzodiazepine receptor ligand PK11195 increased drug (daunomycin)- and fluorochrome (calcein-AM) uptake and induced apoptosis detected by flow cytometry (FCM) technique, DNA electrophoretic analysis and poly(ADP-ribose) polymerase (PARP) cleavage in human multidrug-resistant myeloid leukemia (BL-60/VCR) and ovarian carcinoma (A2780/ADR) cells in vitro. The position of PK11195 with respect to drug-resistance modulator (DRM) efficiency, compared to the reference DRMs with the aid of FCM technique, was as follows: PSC833 > verapamil > PK11195 > vincristine. Our data show up to now not indicated observation that PK11195 possesses multidrug resistance modulating activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

[Is allergy a contraindication for tonsillectomy?].

Many immunologists indicate that tonsillectomy (TE) performed in patients with allergy has an unfavourable impact on the development of allergy and asthma. This warning has significantly decreased the number of TE in children, and resulted in an increase in the occurrence of peritonsillar abscesses, and high incidence of obstructive breathing disturbances during sleep associated with developmental physical and mental consequences in children. The subjective of this study was to find out the influence of TE on the development of allergy in 29 children, in whom their allergy was confirmed 1-5 years after TE. The allergic disease has improved or disappeared in 24 children (82.8%), no changes were recorded in 4 children (13.8%), deterioration has occurred only in 1 child (3.4%) who developed asthma, while in common population, asthma occurs in 10% of children. The results of this study confirm that TE does not have an unfavourable impact on the development of allergy, and therefore allergy does not represent a contraindication for tonsillectomy. (Fig. 1, Ref. 22.)

Asthma↗

PubMed1999

[Auditory screening of neonates using an objective method--otoacoustic emissions].

Screening for hearing loss in children in Slovak republic with non-objective methods detects only deaf children, mean age of the diagnosis establishment is even 2.5 years. It is necessary for healthy child development to detect and treat a child with bilateral defect before 1 year of age. Preliminary results of auditory screening in 456 newborns with objective method of otoacoustic emissions (OAE) proved the necessity of otoacoustic screening in all risk newborns. In one of 204 risk newborns serious hearing loss was proved with BERA examination and in next 8 of them it is suspected according to the OAE results and additional tympanometric examination with the A curve. Until now in newborn without risk of hearing loss in history were not detected bilateral hearing loss, only unilateral, not requiring treatment. (Fig. 1, Tab. 2. Ref. 9.)

Female↗