OBJECTIVE: This study aimed to evaluate the correlation between the expressions of lung resistance protein (LRP), P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP)-1, MRP3, and MRP5 and histopathological parameters and clinical outcome, and to determine the predictive and prognostic value of these transport proteins in patients with ovarian cancer. METHODS: Tumor samples from 111 chemonaive patients with epithelial ovarian cancer who underwent primary surgery from 2006 to 2010 were immunohistochemically stained for LRP, Pgp, MRP1, MRP3, and MRP5 expressions. RESULTS: MRP1 expression was greater among patients with late disease than among patients with early stage ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) I + II, 71.6% (confidence interval, 60-100); FIGO III + IV, 83.6% (confidence interval, 100-100); P = 0.03]. The histological subtype correlated with the expressions of LRP, Pgp, MRP1, and MRP3. Relapse of disease during the next 24 months occurred more often among patients with higher Pgp and MRP1 than among patients with lower Pgp and MRP1 expressions. FIGO stage, histological type, debulking efficiency, strong Pgp expression, and strong MRP1 expression correlated significantly with shorter progression-free survival (log-rank test, P = 0.001, P = 0.004, P = 0.001, P = 0.051, and P = 0.046, respectively). FIGO stage, histological type, debulking efficiency, and strong MRP1 expression correlated with poor patient survival (log-rank test, P = 0.001, P = 0.042, P = 0.005, and P = 0.018, respectively). CONCLUSIONS: Pgp and MRP1 expressions were clinically significant in patients with ovarian cancer. Pgp and MRP1 may be reliable, independent predictive and prognostic factors regarding the clinical outcome of ovarian cancer. MRP3 is less important as a predictive and prognostic factor than MRP1 expression. MRP5 and LRP expressions were not applicable prognostic parameters regarding ovarian cancer.
- MeSH
- analýza přežití MeSH
- chemorezistence * MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory glandulární a epitelové farmakoterapie metabolismus mortalita patologie MeSH
- nádory vaječníků farmakoterapie metabolismus mortalita patologie MeSH
- P-glykoprotein metabolismus MeSH
- prognóza MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vault ribonucleoprotein particles metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- ABC transportéry analýza MeSH
- analýza přežití MeSH
- chemorezistence MeSH
- dospělí MeSH
- hodnocení rizik statistika a číselné údaje MeSH
- karcinom epidemiologie etiologie farmakoterapie patofyziologie MeSH
- léková rezistence MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetná léková rezistence MeSH
- nádory vaječníků * epidemiologie etiologie farmakoterapie patofyziologie MeSH
- P-glykoprotein analýza MeSH
- přežití bez známek nemoci * MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům * analýza MeSH
- senioři MeSH
- vault ribonucleoprotein particles analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
A large number of renal cancer patients show poor or partial response to chemotherapy and the precise mechanism has not been understood yet. MDR is the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs and is associated with the elevated expression of MDR proteins. These are divided into two groups: ABC transporters and non-ABC transporters. The aim of our study was to determine the expression of MDR1/Pgp, MRP1 and LRP in 47 samples of renal cell carcinomas using immunohistochemical assay. Our results were analysed in relation to nuclear grade and other clinical and pathological parameters to see the possible correlation between the expression of MDR proteins and factors mentioned above. The majority of renal carcinoma specimens showed positivity for MDR proteins. In this regard, 21 % of samples revealed positive results for MDR1, 62 % for MRP1 and 76.6 % for LRP protein. Furthermore, our study displayed significant differences between MDR1, LRP and nuclear grade. On the other hand, no association was found between MRP1 and nuclear grade, as well as between the expression of three MDR proteins and other clinically relevant parameters.
- MeSH
- chemorezistence MeSH
- karcinom z renálních buněk metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin metabolismus patologie MeSH
- P-glykoprotein biosyntéza MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům biosyntéza MeSH
- vault ribonucleoprotein particles antagonisté a inhibitory MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
microarrayAims: MRP-1, LRP and TOPO-II are all associated with protection of the cells from the adverse eff ects of variouschemotherapeutics. The aim of this study was to measure the expression of these proteins in Wilms' tumor (WT).Materials and Methods: TMA block was constructed from 14 samples of WT's and from xenografts derived fromthem. Sections of the TMA were used for immunostaining against MRP-1, LRP and TOPO-IIa.Results: All normal kidneys expressed MRP-1 but were either weakly or negatively stained for LRP and TOPO-IIa.In WT samples, MRP-1 was universally expressed, exclusively in the tubular component, while there was no expressionof LRP and TOPO-IIa showed heterogeneous distribution. The xenografts varied in their MRP-1 and TOPO-IIaexpression and exhibited weak/negative staining of LRP.Conclusions: This study shows that although all the proteins evaluated, had diff erent expression patterns in thetumor samples, the most prominent changes in expression were found for MRP-1. The exact clinical implications ofthese changes in expression and their relevance to the resistance of these tumors to chemotherapy requires furtherinvestigation. The fi nding of diff erent expression profi les for the multidrug resistance proteins in the original WT'sand their xenografts suggests that the results of animal cancer models may be diffi cult to interpret.
- MeSH
- čipová analýza tkání metody MeSH
- DNA-topoisomerasy typu II genetika imunologie izolace a purifikace MeSH
- exprese genu genetika imunologie MeSH
- financování organizované MeSH
- imunohistochemie metody využití MeSH
- medicína založená na důkazech MeSH
- modely u zvířat MeSH
- myši inbrední NOD MeSH
- myši SCID MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům genetika imunologie izolace a purifikace MeSH
- vault ribonucleoprotein particles genetika imunologie izolace a purifikace MeSH
- Wilmsův nádor genetika imunologie MeSH
- xenogenní modely - testy protinádorové aktivity metody využití MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
OBJECTIVES: The resistance of tumor cells to cisplatin remains a major cause of treatment failure in cancer patients. In this study, the ability of Pt(IV) complex with adamantylamine-LA-12 and its reduced counterpart with lower oxidation state Pt(II)-LA-9 to overcome intrinsic cisplatin resistance was investigated. METHODS: The ovarian adenocarcinoma SK-OV-3 cells were exposed to cisplatin, LA-9, or LA-12 for 72 h and the effects of drug concentrations that caused 10% or 50% inhibition of cell proliferation were determined. After 24-72 h of sustained exposure viability, apoptosis and inhibition of proliferation were analyzed. DNA synthesis and cell cycle analysis were performed simultaneously in order to determine the modulation of cell cycle after platinum complexes treatment. RESULTS: Lung Resistance-related Protein (LRP/MVP) was detected in SK-OV-3 cells but not in the other two ovarian cancer lines with different sensitivity to cisplatin. LRP/MVP overexpression may be an important factor contributing to intrinsic cisplatin resistance. Interestingly, Pt(IV) complex-LA-12 had approximately 2.7-fold lower IC(50) concentration than LA-9 or cisplatin in SK-OV-3 cells. Moreover, LA-12 caused persistent accumulation of cells in S-phase of the cell cycle while LA-9 and cisplatin treatment-induced S-phase arrest was transient and shifted to G(2)/M-phase at later intervals. Apoptosis seemed to be not the dominant type of cell death caused by such the derivatives, but it was the most intensive after LA-12 treatment. CONCLUSIONS: We found strong differences between effects of Pt(IV) complex-LA-12 and Pt(II) derivatives-LA-9 and cisplatin on cytokinetic parameters. Overall, LA-12 but not its reduced Pt(II) counterpart LA-9 is the compound effective in p53 null human ovarian cancer cells and it is able to overcome intrinsic cisplatin resistance in these cells.
- MeSH
- adenokarcinom farmakoterapie metabolismus patologie MeSH
- amantadin analogy a deriváty aplikace a dávkování MeSH
- buněčný cyklus účinky léků MeSH
- buňky - růstové procesy účinky léků MeSH
- chemorezistence MeSH
- cisplatina aplikace a dávkování MeSH
- DNA nádorová biosyntéza MeSH
- financování organizované MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové proteiny biosyntéza MeSH
- nádory vaječníků farmakoterapie metabolismus patologie MeSH
- organoplatinové sloučeniny aplikace a dávkování farmakologie MeSH
- poly(ADP-ribosa)polymerasy metabolismus MeSH
- protokoly protinádorové kombinované chemoterapie farmakologie MeSH
- vault ribonucleoprotein particles antagonisté a inhibitory MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
