| Id |
Subject |
Object |
Predicate |
Lexical cue |
| TextSentencer_T1 |
0-146 |
Sentence |
denotes |
NCX-4040, a nitric oxide-releasing aspirin, sensitizes drug-resistant human ovarian xenograft tumors to cisplatin by depletion of cellular thiols. |
| TextSentencer_T2 |
147-158 |
Sentence |
denotes |
BACKGROUND: |
| TextSentencer_T3 |
159-252 |
Sentence |
denotes |
Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. |
| TextSentencer_T4 |
253-355 |
Sentence |
denotes |
The high mortality rate is associated with lack of early diagnosis and development of drug resistance. |
| TextSentencer_T5 |
356-485 |
Sentence |
denotes |
The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied. |
| TextSentencer_T6 |
486-723 |
Sentence |
denotes |
METHODS: NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP), was studied in cisplatin-sensitive (A2780 WT) and cisplatin-resistant (A2780 cDDP) cell lines as well as xenograft tumors grown in nude mice. |
| TextSentencer_T7 |
724-820 |
Sentence |
denotes |
Electron paramagnetic resonance (EPR) was used for measurements of nitric oxide and redox state. |
| TextSentencer_T8 |
821-919 |
Sentence |
denotes |
Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies. |
| TextSentencer_T9 |
920-928 |
Sentence |
denotes |
RESULTS: |
| TextSentencer_T10 |
929-1081 |
Sentence |
denotes |
Cells treated with NCX-4040 (25 microM) showed a significant reduction of cell viability (A2780 WT, 34.9 +/- 8.7%; A2780 cDDP, 41.7 +/- 7.6%; p < 0.05). |
| TextSentencer_T11 |
1082-1373 |
Sentence |
denotes |
Further, NCX-4040 significantly enhanced the sensitivity of A2780 cDDP cells (cisplatin alone, 80.6 +/- 11.8% versus NCX-4040+cisplatin, 26.4 +/- 7.6%; p < 0.01) and xenograft tumors (cisplatin alone, 74.0 +/- 4.4% versus NCX-4040+cisplatin, 56.4 +/- 7.8%; p < 0.05), to cisplatin treatment. |
| TextSentencer_T12 |
1374-1553 |
Sentence |
denotes |
EPR imaging of tissue redox and thiol measurements showed a 5.5-fold reduction (p < 0.01) of glutathione in NCX-4040-treated A2780 cDDP tumors when compared to untreated controls. |
| TextSentencer_T13 |
1554-1762 |
Sentence |
denotes |
Immunoblotting analysis of A2780 cDDP tumor xenografts from mice treated with NCX-4040 and cisplatin revealed significant downregulation of pEGFR (Tyr845 and Tyr992) and pSTAT3 (Tyr705 and Ser727) expression. |
| TextSentencer_T14 |
1763-1774 |
Sentence |
denotes |
CONCLUSION: |
| TextSentencer_T15 |
1775-1919 |
Sentence |
denotes |
The results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. |
| TextSentencer_T16 |
1920-2060 |
Sentence |
denotes |
Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies. |
| T1 |
0-146 |
Sentence |
denotes |
NCX-4040, a nitric oxide-releasing aspirin, sensitizes drug-resistant human ovarian xenograft tumors to cisplatin by depletion of cellular thiols. |
| T2 |
147-158 |
Sentence |
denotes |
BACKGROUND: |
| T3 |
159-252 |
Sentence |
denotes |
Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. |
| T4 |
253-355 |
Sentence |
denotes |
The high mortality rate is associated with lack of early diagnosis and development of drug resistance. |
| T5 |
356-485 |
Sentence |
denotes |
The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied. |
| T6 |
486-723 |
Sentence |
denotes |
METHODS: NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP), was studied in cisplatin-sensitive (A2780 WT) and cisplatin-resistant (A2780 cDDP) cell lines as well as xenograft tumors grown in nude mice. |
| T7 |
724-820 |
Sentence |
denotes |
Electron paramagnetic resonance (EPR) was used for measurements of nitric oxide and redox state. |
| T8 |
821-919 |
Sentence |
denotes |
Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies. |
| T9 |
920-928 |
Sentence |
denotes |
RESULTS: |
| T10 |
929-1081 |
Sentence |
denotes |
Cells treated with NCX-4040 (25 microM) showed a significant reduction of cell viability (A2780 WT, 34.9 +/- 8.7%; A2780 cDDP, 41.7 +/- 7.6%; p < 0.05). |
| T11 |
1082-1373 |
Sentence |
denotes |
Further, NCX-4040 significantly enhanced the sensitivity of A2780 cDDP cells (cisplatin alone, 80.6 +/- 11.8% versus NCX-4040+cisplatin, 26.4 +/- 7.6%; p < 0.01) and xenograft tumors (cisplatin alone, 74.0 +/- 4.4% versus NCX-4040+cisplatin, 56.4 +/- 7.8%; p < 0.05), to cisplatin treatment. |
| T12 |
1374-1553 |
Sentence |
denotes |
EPR imaging of tissue redox and thiol measurements showed a 5.5-fold reduction (p < 0.01) of glutathione in NCX-4040-treated A2780 cDDP tumors when compared to untreated controls. |
| T13 |
1554-1762 |
Sentence |
denotes |
Immunoblotting analysis of A2780 cDDP tumor xenografts from mice treated with NCX-4040 and cisplatin revealed significant downregulation of pEGFR (Tyr845 and Tyr992) and pSTAT3 (Tyr705 and Ser727) expression. |
| T14 |
1763-1774 |
Sentence |
denotes |
CONCLUSION: |
| T15 |
1775-1919 |
Sentence |
denotes |
The results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. |
| T16 |
1920-2060 |
Sentence |
denotes |
Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies. |