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Differential Mitochondrial Scoring Associated With Chemotherapeutic Effect On Ovarian Cancer

S. Isonishi, R. Matsumoto,M. Hirama,K. Ochiai,T. Tachibana, H. Ishikawa,M. Yasuda, T. Tanaka

JOURNAL OF CLINICAL ONCOLOGY(2009)

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摘要
e16514 Background: We reported mitochondrial (MT) scoring system related to platinum response in ovarian cancer (OC) (Oncol Rep2008). We investigated whether the system could be useful to evaluate cellular drug sensitivity and patients’ prognosis. Methods: Ultrathin sections of surgical specimens prepared from 41 OC patients were examined by electron microscopy. Ovarian carcinoma cell line 2008 and its platinum- or taxane-resistant variant C13 or PX24 were used as control cells. Seven independent MT features including diameter and pattern of cresta structure were examined. Clinical response and in vitro sensitivity to platinum (P), taxane (T), irrinotecan (CPT), and doxorubicine (D) were examined while the MT scoring was performed independently. Results: Of 41 cases, 37 were available for clinical evaluation (stage II-IV, received 6 cycles of TP chemotherapy). Fifteen cases were responsive, while 22 were resistant. Total MT score in 15 responsive cases was 5.13 ± 1.13 (M ± SE) and was 11.41 ± 0.43 in 22 resistant cases (p < 0.001). Receptor operative characteristics (ROC) analysis revealed that resistant total “cut-off” score was ≥ 10 points (p < 0.05; AUC = 0.86). Except for D, the scoring system well related to P, T, and CPT sensitivity (p; <0.001, <0.001, 0.006). ROC analysis revealed resistant “cut-off” score for P, T and CPT were ≥ 11, 5, and 10 points (p < 0.05; AUC > 0.80). With a median follow up of 20 months, 11 patients have relapsed. The progression-free survival (PFS) curves show a difference in favor of low scoring group of patients (N = 14) compared to high scoring group (N = 19) (hazard ratio 3.99, p = 0.045), corresponding to an absolute difference in 6-months PFS 16% (89 vs 73%). Conclusions: This MT scoring system excellently related to clinically diagnosed P sensitivity as well as cellular sensitivity to P, T and CPT. Each drug has its own specific “cut-off” score, suggesting that the MT function might be differentially involved in drug sensitivity. No significant financial relationships to disclose.
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关键词
ovarian cancer,differential mitochondrial scoring,chemotherapeutic effect
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