Neuroblastoma represents 8-10 % of all malignant tumors in childhood and is responsible for 15 % of cancer deaths in the pediatric population. Aggressive neuroblastomas are often resistant to chemotherapy. Canonically, neuroblastomas can be classified according to the MYCN (N-myc proto-oncogene protein) gene amplification, a common marker of tumor aggressiveness and poor prognosis. It has been found that certain compounds with chelating properties may show anticancer activity, but there is little evidence for the effect of chelators on neuroblastoma. The effect of new chelators characterized by the same functional group, designated as HLZ (1-hydrazino phthalazine), on proliferation (WST-1 and methylene blue assay), cell cycle (flow cytometry), apoptosis (proliferation assay after use of specific pharmacological inhibitors and western blot analysis) and ROS production (fluorometric assay based on dichlorofluorescein diacetate metabolism) was studied in three neuroblastoma cell lines with different levels of MYCN amplification. The molecules were effective only on MYCN-non-amplified cells in which they arrested the cell cycle in the G0/G1 phase. We investigated the mechanism of action and identified the activation of cell signaling that involves protein kinase C.
- MeSH
- apoptóza MeSH
- chelátory farmakologie terapeutické užití MeSH
- dítě MeSH
- jaderné proteiny genetika MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- neuroblastom * farmakoterapie MeSH
- onkogenní proteiny * genetika metabolismus farmakologie MeSH
- proliferace buněk MeSH
- protoonkogen n-myc genetika metabolismus terapeutické užití MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chelátory MeSH
- jaderné proteiny MeSH
- onkogenní proteiny * MeSH
- protoonkogen n-myc MeSH
Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.
- MeSH
- fosfohydroláza PTEN genetika MeSH
- hyperplazie endometria genetika MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- mutace genetika MeSH
- mutační analýza DNA MeSH
- mutační rychlost MeSH
- nádory endometria genetika MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Slovenská republika MeSH
- Názvy látek
- fosfohydroláza PTEN MeSH
- PTEN protein, human MeSH Prohlížeč