Correlation between Extreme Drug Resistance Assay and Response to Primary Paclitaxel and Cisplatin in Patients with Epithelial Ovarian Cancer

1998 ◽  
Vol 70 (3) ◽  
pp. 392-397 ◽  
Author(s):  
Gamal H. Eltabbakh ◽  
M.Steven Piver ◽  
Ronald E. Hempling ◽  
Fernando O. Recio ◽  
Shashikant B. Lele ◽  
...  
2009 ◽  
Vol 114 (2) ◽  
pp. 246-252 ◽  
Author(s):  
Amer K. Karam ◽  
Jing Wang Chiang ◽  
Ewina Fung ◽  
Vladimir Nossov ◽  
Beth Y. Karlan

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5504-5504
Author(s):  
A. Karam ◽  
J. Wang Chiang ◽  
E. Fung ◽  
V. Nossov ◽  
B. Y. Karlan

5504 Background: Extreme drug resistance (EDR) assays have been used as tools in identifying those agents that are least likely to be of clinical benefit in the treatment of epithelial ovarian cancer (EOC). We sought to examine the effect of obtaining EDR assays on the outcome of patients with EOC in the primary and recurrent setting. Methods: We conducted a retrospective review of demographic, pathologic, EDR assay and outcome data from 377 patients with EOC who had an assay sent at the time of their diagnosis or at recurrence. Univariate followed by multivariate analyses using Cox proportional hazards method were performed to identify and estimate the impact of independent prognostic factors on time to progression (TTP), overall survival (OS) and survival after recurrence (RS). Results: Increasing age was associated with a worse OS and RS (HR = 1.34; 95% CI, 1.14–1.58 and HR = 1.14; 95% CI, 1.00–1.31, for each decade increase in age respectively). Compared with patients with microscopic residual disease, patients who were left with 0.1 to 1.0 cm and >1.0 cm residual disease had an increased risk of recurrence (HR=1.94; 95% CI, 1.33 to 2.84 and HR=3.61; 95% CI; 2.07 to 6.39, respectively) and death (HR = 1.59; 95% CI, 1.03 to 2.45; and HR = 2.14; 95% CI, 1.09 to 4.20, respectively). For patients who recurred, those who did not undergo secondary cytoreductive surgery and patients who were left with >1.0 cm residual had an increased risk of death compared to patients with microscopic residual (HR = 2.13; 95% CI, 1.28 to 3.54; and HR = 2.84; 95% CI, 1.71 to 4.71, respectively). EDR assay results for single agents or combinations did not independently predict patient outcomes. Conclusions: The amount of residual disease continues to be an important prognostic factor, especially when all macroscopic disease is removed both in the primary and recurrent setting. Increasing age is also an independent predictor of OS and RS. EDR assay results do not independently predict or alter the outcomes of patients with EOC who are treated with the current standard of care including optimal cytoreductive surgery followed by platinum and taxane combination chemotherapy in either the primary or recurrent setting. No significant financial relationships to disclose.


Author(s):  
Bahire Kucukkaya ◽  
Demet Erdag ◽  
Fahri Akbas ◽  
Leman Yalcintepe

Aim: Anticancer drugs (chemotherapeutics) used in cancer treatment (chemotherapy) lead to drug resistance. This study was conducted to investigate the possible effect of iron on calcium homeostasis in epithelial ovarian cancer cells (MDAH-2774) and cisplatin-resistant cells of the same cell line (MDAH-2774/DDP). Methods: To develop MDAH-2774/DDP cells, MDAH-2774 (MDAH) cells were treated with cisplatin in dose increases of 5 μM between 0 μM and 70 μM. The effect of iron on the viability of MDAH and MDAH/DDP cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test at the end of 24 h incubation. Results: At increasing iron concentrations in MDAH and MDAH/DDP cells, the mRNA gene of fifteen genes [inositol 1,4,5-triphosphate receptor (IP3R)1/2/3, ryanodine receptor (RYR)1/2, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)1/2/3, Na+/Ca2+ exchange (NCX)1/2/3, and plasma membrane Ca2+ ATPase (PMCA)1/2/3/4] associated with Ca2+ differences in expression were determined by quantitative reverse transcription-polymerase chain reaction. Changes in IP3R2, RYR1, SERCA2, NCX3, PMCA1, and PMCA3 gene expressions were observed in iron treatment of MDAH/DDP cells, while changes were detected in iron treatment of MDAH cells in IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX2/3, and PMCA1 expressions. Conclusions: This changes in the expression of calcium channels, pumps, and exchange proteins in the epithelial ovarian cancer cell line and in cisplatin-resistant epithelial ovarian cancer cells suggest that iron may have an important role in regulating calcium homeostasis. Due to differences in the expression of genes that play of an important role in the regulation of calcium homeostasis in the effect of iron, drug resistance can be prevented by introducing a new perspective on the use of inhibitors and activators of these genes and thus cytostatic treatment strategies.


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