Fibrates protect against vascular endothelial dysfunction induced by paclitaxel and carboplatin chemotherapy for cancer patients: a pilot study
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| 024 | 7 | 0 | |a 10.1007/s10147-014-0779-y |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s10147-014-0779-y | ||
| 245 | 0 | 0 | |a Fibrates protect against vascular endothelial dysfunction induced by paclitaxel and carboplatin chemotherapy for cancer patients: a pilot study |h [Elektronische Daten] |c [Ayako Watanabe, Akiko Tanabe, Risa Maruoka, Kiyoko Nakamura, Koji Hatta, Yoshihiro Ono, Yoshito Terai, Masahide Ohmichi] |
| 520 | 3 | |a Background: Although we previously demonstrated that paclitaxel and carboplatin chemotherapy (TCchem) is associated with vascular toxicities, the underlying mechanisms remain unclear. Cisplatin is known to inhibit PPARα following microvascular damage to the kidneys. The primary aim of this study was to evaluate whether TCchem induces vascular endothelial dysfunction via systemic PPARα deficiency. In addition, human umbilical vein endothelial cells (HUVECs) were used to elucidate the mechanisms responsible for TCchem-induced vascular toxicities. Methods: This study enrolled 45 gynecological cancer patients with normal lipid profiles who underwent surgical treatment followed by TCchem. The elevated triglyceride (TG) group included patients (n=19) who exhibited hypertriglyceridemia during TCchem, and the stable TG group (n=15) included patients with a normal TG level. Eleven patients exhibiting hypertriglyceridemia during TCchem were administered bezafibrate (fibrate group). Endothelial dysfunction was evaluated based on flow-mediated dilation (FMD) values and serum pentraxin-3 levels measured before TCchem and immediately after the final TCchem. HUVECs were used to elucidate the biological mechanisms underlying the endothelial dysfunction induced by TCchem. Results: The administration of TCchem induced hypertriglyceridemia in 66 percent of the participants, and bezafibrate reduced the serum TG levels. Meanwhile, the decrease in flow-mediated dilatation (%FMD) induced by TCchem improved following treatment with bezafibrate. The serum pentraxin-3 level increased rapidly after TCchem and decreased following bezafibrate treatment. An in vitro examination demonstrated TCchem attenuated nitric oxide production and PPARα activity in HUVECs, which was partially improved by treatment with bezafibrate. Conclusion: Bezafibrate prevents endothelial dysfunction induced by TCchem via TG-dependent and TG-independent mechanisms. | |
| 540 | |a Japan Society of Clinical Oncology, 2014 | ||
| 690 | 7 | |a Bezafibrate |2 nationallicence | |
| 690 | 7 | |a Platinum-based chemotherapy |2 nationallicence | |
| 690 | 7 | |a Carboplatin |2 nationallicence | |
| 690 | 7 | |a Paclitaxel |2 nationallicence | |
| 690 | 7 | |a Gynecological cancer |2 nationallicence | |
| 690 | 7 | |a Triglyceride |2 nationallicence | |
| 690 | 7 | |a FMD |2 nationallicence | |
| 690 | 7 | |a PtChem : Platinum-based chemotherapy |2 nationallicence | |
| 690 | 7 | |a TG : Triglycerides |2 nationallicence | |
| 690 | 7 | |a TCchem : Paclitaxel and carboplatin combination chemotherapy |2 nationallicence | |
| 690 | 7 | |a FMD : Flow-mediated dilation |2 nationallicence | |
| 690 | 7 | |a PPARα : Peroxisome proliferator-activated receptor-α |2 nationallicence | |
| 690 | 7 | |a OC : Ovarian cancer |2 nationallicence | |
| 690 | 7 | |a EC : Endometrial cancer |2 nationallicence | |
| 690 | 7 | |a CVD : Cardiovascular disease |2 nationallicence | |
| 690 | 7 | |a LDL : Low-density lipoprotein |2 nationallicence | |
| 690 | 7 | |a HDL : High-density lipoprotein |2 nationallicence | |
| 690 | 7 | |a hsCRP : High-sensitivity C-reactive protein |2 nationallicence | |
| 690 | 7 | |a CDDP : Cisplatin |2 nationallicence | |
| 690 | 7 | |a CBDCA : Carboplatin |2 nationallicence | |
| 690 | 7 | |a PTX : Paclitaxel |2 nationallicence | |
| 700 | 1 | |a Watanabe |D Ayako |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | |
| 700 | 1 | |a Tanabe |D Akiko |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | |
| 700 | 1 | |a Maruoka |D Risa |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | |
| 700 | 1 | |a Nakamura |D Kiyoko |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | |
| 700 | 1 | |a Hatta |D Koji |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | |
| 700 | 1 | |a Ono |D Yoshihiro |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | |
| 700 | 1 | |a Terai |D Yoshito |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | |
| 700 | 1 | |a Ohmichi |D Masahide |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | |
| 773 | 0 | |t International Journal of Clinical Oncology |d Springer Japan |g 20/4(2015-08-01), 829-838 |x 1341-9625 |q 20:4<829 |1 2015 |2 20 |o 10147 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s10147-014-0779-y |q text/html |z Onlinezugriff via DOI |
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| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s10147-014-0779-y |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Watanabe |D Ayako |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Tanabe |D Akiko |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Maruoka |D Risa |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Nakamura |D Kiyoko |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hatta |D Koji |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ono |D Yoshihiro |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Terai |D Yoshito |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ohmichi |D Masahide |u Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t International Journal of Clinical Oncology |d Springer Japan |g 20/4(2015-08-01), 829-838 |x 1341-9625 |q 20:4<829 |1 2015 |2 20 |o 10147 | ||