scholarly journals Drug resistance features and S-phase fraction as possible determinants for drug response in a panel of human ovarian cancer xenografts

2000 ◽  
Vol 83 (7) ◽  
pp. 921-927 ◽  
Author(s):  
G M Kolfschoten ◽  
T M Hulscher ◽  
H M Pinedo ◽  
E Boven
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Drug Response ◽  
S Phase ◽  
Phase Fraction ◽  
Human Ovarian Cancer

scholarly journals S-Phase Cell Cycle Arrest, Apoptosis, and Molecular Mechanisms of Aplasia Ras homolog Member I–Induced Human Ovarian Cancer SKOV3 Cell Lines

2014 ◽  
Vol 24 (4) ◽  
pp. 629-634 ◽  
Author(s):  
Qiaoying Zhu ◽  
Jianming Hu ◽  
Huijuan Meng ◽  
Yufei Shen ◽  
Jinhua Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Significant Inhibition ◽  
S Phase ◽  
Phase Cell ◽  
Cell Cycle Distribution ◽  
Human Ovarian Cancer ◽  
Skov3 Cell ◽  
Skov3 Cells

ObjectiveAplasia Ras homolog member I (ARHI) is associated with human ovarian cancer (HOC) growth and proliferation; however, the mechanisms are unclear. The purpose of this study was to investigateARHIeffects in HOC SKOV3 cells.MethodsWe transfected SKOV3 cells with PIRES2-EGFP-ARHI and measured growth inhibition rates, cell cycle distribution, apoptosis rates, and expression of P-STAT3 (phosphorylated signal transduction and activators of transcription 3) and P-ERK (phosphorylated extracellular signal regulated protein kinase).ResultsOur data showed significant inhibition of growth, significantly increased S-phase arrest and apoptosis rates, and reduction of P-STAT3 and P-ERK1/2 expression levels.ConclusionsWe propose the mechanism may involveARHI-induced phosphorylation of ERK1/2 and STAT3 protein kinases, thereby blocking proliferation signaling pathways, to induce HOC SKOV3 apoptosis.

Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced ovarian cancer

1993 ◽  
Vol 3 (5) ◽  
pp. 271-278 ◽  
Author(s):  
G. Scambia ◽  
Benedetti P. Panici ◽  
G. Ferrandina ◽  
F. Battaglia ◽  
G. Baiocchi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
S Phase ◽  
Phase Fraction ◽  
Dna Index ◽  
Free Survival ◽  
Time To Recurrence ◽  
Her 2 ◽  
Tumor Ploidy

The immunohistochemical expression of HER-2/neu and cytofluorimetric data were retrospectively analyzed in a group of primary advanced ovarian cancers. Thirty-three out of 94 (35%) cases showed a specific p185/neu immunoreaction. No correlation between p185/neu expression and any of the clinico-pathologic parameters examined was observed. As far as cytofluorimetric data are concerned, 38 out of 69 (55%) of the tumors were diploid (DNA index = 1) while 31 (45%) were aneuploid (DNA index from 1.10 to 2.50 with a median value of 1.50). Ovarian tumors were defined as of low and high S-phase fraction in 68% and 32% of the cases, respectively. Tumor ploidy and S-phase fraction did not correlate with the clinico-pathologic characteristics or p185/neu oncoprotein expression. Aneuploid tumors had a higher S-phase fraction (mean: 15.81 ± 13.44) than diploid tumors (mean: 8.89 ± 7.98) (P< 0.01). p185/neu expression failed to affect significantly both overall and progression free survival. On the other hand tumor ploidy was found to be related to the prognosis of advanced ovarian cancer patients although the difference was not statistically significant. As far as progression free survival is concerned, the median time to recurrence was not reached for diploid cases whereas it was 21 months for aneuploid cases (P< 0.05). The 5-year survival for patients with a low S-phase fraction (58%) was significantly higher than for patients with high S-phase fraction tumors (28%) (P< 0.01). Median time to recurrence was 48 and 17 months for low and high S-phase fraction tumor patients, respectively (P< 0.05). However, in a multivariate analysis both tumor ploidy and S-phase fraction did not retain their prognostic value. The assessment of the role of the parameters examined in improving the prognostic characterization of ovarian cancer patients should be investigated in large multicenter clinical trials.

scholarly journals The modulatory effect of green tea catechin on drug resistance in human ovarian cancer cells

2019 ◽  
Vol 28 (5) ◽  
pp. 657-667 ◽  
Author(s):  
Dawid Przystupski ◽  
Olga Michel ◽  
Joanna Rossowska ◽  
Stanisław Kwiatkowski ◽  
Jolanta Saczko ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Green Tea ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Green Tea Catechin

Correlation between immunohistochemical biomarker expression and in vitro drug response factors in stage III-IV ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16055-16055
Author(s):  
O. Tawfik ◽  
L. Peterson ◽  
R. Parker ◽  
E. Mechetner ◽  
M. Davis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Clinical Outcome ◽  
Drug Response ◽  
Chemotherapeutic Agents ◽  
Stage Iii ◽  
Prior Chemotherapy ◽  
Egfr Expression ◽  
Mib 1

16055 Background: The reliability of molecular biomarkers as predictors of treatment outcome remains unclear and, in relation to drug resistance even less is known. Immunohistochemical (IHC) expression of biomarkers and in vitro drug resistance (IVDR) relative to clinical outcome were evaluated in patients with stage III-IV epithelial ovarian cancer (OC) who received combination carboplatin (CAR) plus paclitaxel (TAX) chemotherapy. Methods: We correlated clinical outcome with histopathology and biomarker expression of MIB-1, p53, BCL2, EGFR, ER and PR in 98 OC patients with tumors tested for IVDR by extreme drug resistance (EDR) assay. IVDR was determined following exposures to single agents CAR, cisplatin (CP), TAX, taxotere (TXT), gemcitabine (GCB), topotecan (TP), liposomil doxorubicin, and cytoxan (CT). Percentage cell growth inhibition (PCI) for each drug was compared with PCI from untreated control cultures. Results: Tumors with prior chemotherapy (n=29) were more resistant to CAR (unpaired t-test, p=0.046), and CT (p=0.038), and more sensitive to liposomil doxorubicin (p=0.009), compared to treatment naive tumors (n=53). For 65 tumors, there was a positive relationship between MIB-1 vs p53 (r=0.419; p=0.001), and between ER vs PR (r=0.339; p=0.011). Correlation between biomarkers and drug response showed a significantly inverse relationship between MIB-1 vs liposomil doxorubicin, p53 vs liposomil doxorubicin, EGFR vs CAR, CP, GCB and TAX; and between ER vs TXT and CT, and PR vs CT and TP. With a 53% (33/61) response rate to CAR+TAX, time to progression (TTP) for responders (R) with EGFR+ tumors was longer (median TTP 15.6 mo); and shorter for R with EGFR- tumors (p=0.008). For R and non-R, BCL2+ tumors had longer overall survival (OS) (median OS 23.3 mo; p=0.006). No other significant correlations were seen. Conclusion: Prior chemotherapy increased IVDR to CAR and CT, and increased sensitivity to liposomil doxorubicin. Increased expression of proliferation biomarkers, particularly EGFR, correlated with resistance to several chemotherapeutic agents. EGFR expression in responders was associated with longer TTP. The significance of in vitro correlates of prognostic biomarker expression and IVDR for predicting chemoresistance warrants prospective studies to assess its value in clinical settings. [Table: see text]

Superparamagnetic Iron Oxide Nanoparticles Induce Ferroptosis of Human Ovarian Cancer Stem Cells by Weakening Cellular Autophagy

2020 ◽  
Vol 16 (11) ◽  
pp. 1612-1622
Author(s):  
Yongyi Huang ◽  
Jiajia Lin ◽  
Ying Xiong ◽  
Juan Chen ◽  
Xiling Du ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ovarian Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Superparamagnetic Iron Oxide ◽  
Oxide Nanoparticles ◽  
Human Ovarian Cancer ◽  
Ovarian Cancer Stem Cells

Human ovarian cancer stem cells (HuOCSCs) are the main source of ovarian cancer recurrence, metastasis, and drug resistance. Superparamagnetic iron oxide nanoparticles (SPIONs) are well-known nucleic acid or drug carriers owing to their controllable properties, superior stability, and easy modification. However, whether SPIONs can inhibit the activity of HuOCSCs by inducing ferroptosis remains unclear. In the present study, we isolated CD44+ /CD133+ HuOCSCs from tumours of four patients with clear cell ovarian cancer and added 0.2 mM SPIONs for mixed culture. Transmission electron microscopy showed that SPION-treated HuOCSCs contained multiple high-density electron clouds. Prussian blue staining showed high concentrations of iron ions in the cells. In vitro , SPIONs treatment of HuOCSCs inhibited cell proliferation, migration, and soft agar clone formation, weakened their resistance to multiple chemotherapeutics, and induced cell death. In vivo , SPIONs pretreatment of HuOCSCs significantly reduced their tumour-forming ability and induced angiogenesis in nude mice. Further, SPIONs induced the accumulation of reactive oxygen species in HuOCSCs and induced oxidative stress. qPCR analysis indicated that SPIONs-treated HuOCSCs had reduced expression of tumour stem cell markers (CD117, NANOG, CD133, and SOX2), cell proliferation factors (KI67, CCND), autophagy-related factors (ATG3, ATG5, MAP1ALC3a, MAP1ALC3b, and MAP1ALC3c), and certain negative regulators of ferroptosis, while the mRNA expression levels of cell death-related proteins (BAK1 and BID), and certain positive regulators of ferroptosis were significantly increased. Overall, our findings suggest that SPIONs induce oxidative stress and decrease autophagy activity in ovarian cancer stem cells, activate ferroptosis, and inhibit their proliferation, invasion, drug resistance, and tumorigenic ability.

scholarly journals S-Phase Fraction and DNA Content Determined by Use of Laser Scanning Cytometry in Ovarian Cancer Patients

2012 ◽  
Vol 138 (suppl 1) ◽  
pp. A270-A270
Author(s):  
Alica Galbava ◽  
Stefan Galbavy ◽  
Lubos Danisovic ◽  
Stefan Polak
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Dna Content ◽  
Laser Scanning ◽  
S Phase ◽  
Phase Fraction ◽  
Laser Scanning Cytometry

scholarly journals Erratum to: microRNA 490-3P enhances the drug-resistance of human ovarian cancer cells

2015 ◽  
Vol 8 (1) ◽  
Author(s):  
Shuo Chen ◽  
Xi Chen ◽  
Yin-Ling Xiu ◽  
Kai-Xuan Sun ◽  
Zhi-Hong Zong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer

Inhibition of JAK2 Reverses Paclitaxel Resistance in Human Ovarian Cancer Cells

2015 ◽  
Vol 25 (9) ◽  
pp. 1557-1564 ◽  
Author(s):  
Yefang Xu ◽  
Jingjing Zhang ◽  
Jing Wu ◽  
Sheng Zhong ◽  
Hongxia Li
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Kinase Inhibitor ◽  
Human Ovarian Cancer ◽  
Multidrug Resistance Protein ◽  
Paclitaxel Resistance ◽  
Multidrug Resistance Protein 1 ◽  
Ovarian Cancers ◽  
Resistance Protein ◽  
Resistance To Chemotherapy

ObjectiveResistance to chemotherapy is a major factor that limits the postsurgical survival of ovarian cancer patients. Janus-activated kinase 2 (JAK2) has been implicated in cancer cell survival and the development of drug resistance in ovarian cancers. In the present study, we sought to determine whether inhibition of JAK2 reverses drug resistance in OC3/TAX300 cells, a paclitaxel-resistant human ovarian cancer cell line previously established in our laboratory.MethodsOC3/TAX300 cells were transduced with lentivirus expressing small interference RNA (siRNA) against JAK2 and treated with JAK2 kinase inhibitor AG490.ResultsTreatment with JAK2-siRNA markedly decreased the messenger RNA and protein of JAK2 as determined by real-time polymerase chain reaction and Western blot analysis. OC3/TAX300 cells treated with JAK2-siRNA exhibited stalled growth, increased cell cycle arrest in G2/M phase, and enhanced apoptosis in response to paclitaxel. In keeping with this, JAK2-siRNA also inhibited the expression of multidrug resistance protein 1. To determine whether JAK2 promotes paclitaxel resistance via phosphorylation of signal transducer and activator of transcription 3 (STAT3), a transcription factor known to be involved in resistance to chemotherapy, we treated OC3/TAX300 cells with JAK2 kinase inhibitor AG490. Of note, AG490 reduced the level of p-STAT3 and inhibited the expression of multidrug resistance protein 1 in a dose-dependent manner.ConclusionsCollectively, we conclude that the JAK2-STAT3 pathway promotes the development of paclitaxel resistance via upregulating the expression of prosurvival and antiapoptotic genes. Targeting this pathway may be effective in reversing resistance to chemotherapy in ovarian cancers.

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