The aim of our study was to determine the effect of selected cytostatics on a human ovarian cancer cell line A2780 as a model system for ovarian cancer treatment. This cell line is considered cisplatin-sensitive. Panel of tested cytostatics included cisplatin, paclitaxel, carboplatin, gemcitabine, topotecan and etoposide. These cytostatics have a different mechanism of action. To evaluate cytotoxic potential of the tested compounds, the methods measuring various toxicological endpoints were employed including morphological studies, MTT assay, dynamic monitoring of cell proliferation with xCELLigence, cell cycle analysis, caspase 3 activity and expression of proteins involved in cell cycle regulation and cell death. The A270 cell line showed different sensitivity towards the selected cytostatics, the highest cytotoxic effect was associated with paclitaxel and topotecan., Kateřina Caltová, Miroslav Červinka, and Literatura 38
Antracykliny patřily dlouhou dobu mezi základní léky v adjuvantní, neoadjuvantní i paliativní terapii karcinomu prsu. Jejich indikace byla založena na vysoké účinnosti. V posledních letech se však objevuje řada skutečností, které zcela mění pohled na postavení antracyklinů. Především jsou to obavy z významné kardiotoxicity, incidence sekundárních malignit – leukemií a neúčinnost u pacientek s HER2 a TOPO2 negativními tumory. Pro a proti užití antracyklinů u karcinomu prsu jsou shrnuty v následujícím článku., Anthracyclins ranked among the basic drugs used in the adjuvant, neoadjuvant as far as in paliative treatment of breast cancer for a long time. Their indication was based on a high eficacy. However, lot of circumstances appeared within the last years which totally change our view on the anthracyclins position. First of all there is a fear of significant cardiotoxicity, the incidence of secondary malignancies – leucemias and ineffectivnes in patients with HER2 and TOPO2 negative tumors. Pros and cons of the anthracycline use in breast cancer are summarised in the following article., Tomáš Svoboda, and Lit.: 12
One of the significant limiting complications of paclitaxel is
painful peripheral neuropathy during its therapy for several types
of cancers. Our recent study showed that impairment of
Nrf2-antioxidant response element (Nrf2-ARE) and upregulation
of oxidative signals in the dorsal root ganglion (DRG) of rats with
treatment of paclitaxel result in neuropathic pain. The purpose of
this study was to examine the beneficial role played by
electroacupuncture (EA) in modifying neuropathic pain evoked by
paclitaxel via Nrf2-ARE and oxidative mechanisms. Behavioral
test was performed to determine mechanical and thermal
sensitivity in rats. Western Blot analysis and ELISA were used to
examine expression of Nrf2-ARE and superoxide dismutases
(SOD); and the levels of products of oxidative stress in the DRG.
Our data showed that paclitaxel increased mechanical and
thermal sensitivity and this was accompanied with impaired
Nrf2-ARE and SOD in the DRG and amplified products of
oxidative stress (i.e. 8-isoprostaglandin F2α and 8-hydroxy-2’-
deoxyguanosine). EA treatment largely restored the levels of
Nrf2-ARE/SOD and inhibited products of oxidative stress and
thereby attenuated mechanical and thermal hypersensitivity
induced by paclitaxel. In conclusion, we revealed specific
signaling pathways leading to paclitaxel-evoked neuropathic pain,
including impairment of Nrf2-ARE and heightened oxidative
signals. We further provided evidence for the role of EA in
alleviating paclitaxel-neuropathic pain via these molecular
mediators.
Paclitaxel is used for the treatment of several types of cancers.
However, one of the significant limiting complications of
paclitaxel is painful peripheral neuropathy during its therapy. In
this study we examined the engagement of antioxidative signal
pathway of the dorsal root ganglion (DRG) in mechanical and
thermal hypersensitivity evoked by paclitaxel. Behavioral test was
performed to determine mechanical and thermal sensitivity in
rats. Western blot analysis and ELISA were used to examine
expression of Nrf2-antioxidant response element (ARE) and
superoxide dismutases (SOD); and the levels of products of
oxidative stress in the DRG. Our results show that paclitaxel
increased mechanical and thermal sensitivity as compared with
vehicle control animals. Paclitaxel also impaired Nrf2-ARE and
SOD in the DRG and amplified products of oxidative stress,
namely 8-isoprostaglandin F2α and 8-hydroxy-2’-
deoxyguanosine. Systemic administration of SOD mimetic using
tempol, antioxidant vitamin C or blocking oxidative pathway
using NADPH oxidase inhibitor (GKT137831) attenuated
mechanical and thermal hypersensitivity induced by paclitaxel.
This inhibitory effect was accompanied with decreases of
proinflammatory cytokines (PICs) such as IL-1β, IL-6 and TNF-α
in the DRG. In conclusion, the data revealed impairment of
Nrf2-ARE and heightened oxidative and PIC signals in the DRG of
paclitaxel rats, leading to neuropathic pain. Balancing of reactive
oxygen species by supplying antioxidants and/or inhibiting
NADPH oxidase appears significant to yield beneficial effects in
neuropathic pain conditions after chemotherapeutic paclitaxel.