Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug
Implantation of self-expanding metal stents (SEMS) is palliation for patients suffering from inoperable malignant obstructions associated with biliary and pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed because SEMS are susceptible to occlusion by tumor in-growth. We re...
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| Format: | Article |
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Wiley
2015-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2015/568981 |
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| author | Sookhee Bang Sung Ill Jang Su Yeon Lee Yi-Yong Baek Jieun Yun Soo Jin Oh Chang Woo Lee Eun Ae Jo Kun Na Sugeun Yang Don Haeng Lee Dong Ki Lee |
| author_facet | Sookhee Bang Sung Ill Jang Su Yeon Lee Yi-Yong Baek Jieun Yun Soo Jin Oh Chang Woo Lee Eun Ae Jo Kun Na Sugeun Yang Don Haeng Lee Dong Ki Lee |
| author_sort | Sookhee Bang |
| collection | DOAJ |
| description | Implantation of self-expanding metal stents (SEMS) is palliation for patients suffering from inoperable malignant obstructions associated with biliary and pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed because SEMS are susceptible to occlusion by tumor in-growth. We reported recently that paclitaxel-eluting SEMS provide enhanced local drug delivery in an animal model. However, little is known about the molecular mechanisms by which paclitaxel-eluting stents attenuate tumor growth. We investigated the signal transduction pathways underlying the antiproliferative effects of a paclitaxel-eluting membrane (PEM) implanted in pancreatic/cholangiocarcinoma tumor bearing nude mice. Molecular and cellular alterations were analyzed in the PEM-implanted pancreatic/cholangiocarcinoma xenograft tumors by Western blot, immunoprecipitation, and immunofluorescence. The quantities of paclitaxel released into the tumor and plasma were determined by liquid chromatography-tandem mass spectroscopy. Paclitaxel from the PEM and its diffusion into the tumor inhibited angiogenesis, which involved suppression of mammalian target of rapamycin (mTOR) through regulation of hypoxia inducible factor (HIF-1) and increased apoptosis. Moreover, implantation of the PEM inhibited tumor-stromal interaction-related expression of proteins such as CD44, SPARC, matrix metalloproteinase-2, and vimentin. Local delivery of paclitaxel from a PEM inhibited growth of pancreatic/cholangiocarcinoma tumors in nude mice by suppressing angiogenesis via the mTOR and inducing apoptosis signal pathway. |
| format | Article |
| id | doaj-art-46a906c6a7c54aefa033b921e8bf8d6e |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-46a906c6a7c54aefa033b921e8bf8d6e2025-02-03T01:29:15ZengWileyGastroenterology Research and Practice1687-61211687-630X2015-01-01201510.1155/2015/568981568981Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old DrugSookhee Bang0Sung Ill Jang1Su Yeon Lee2Yi-Yong Baek3Jieun Yun4Soo Jin Oh5Chang Woo Lee6Eun Ae Jo7Kun Na8Sugeun Yang9Don Haeng Lee10Dong Ki Lee11Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul 135-720, Republic of KoreaDepartment of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul 135-720, Republic of KoreaDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul 135-720, Republic of KoreaDepartment of Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Republic of KoreaDepartment of Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Republic of KoreaDepartment of Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Republic of KoreaDepartment of Research and Development, Taewoong Medical Co., Gimpo, Republic of KoreaDepartment of Biotechnology, The Catholic University, Bucheon, Republic of KoreaDepartment of New Drug Development, School of Medicine, Inha University, Incheon, Republic of KoreaDepartment of Internal Medicine, School of Medicine, Inha University, Incheon, Republic of KoreaDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul 135-720, Republic of KoreaImplantation of self-expanding metal stents (SEMS) is palliation for patients suffering from inoperable malignant obstructions associated with biliary and pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed because SEMS are susceptible to occlusion by tumor in-growth. We reported recently that paclitaxel-eluting SEMS provide enhanced local drug delivery in an animal model. However, little is known about the molecular mechanisms by which paclitaxel-eluting stents attenuate tumor growth. We investigated the signal transduction pathways underlying the antiproliferative effects of a paclitaxel-eluting membrane (PEM) implanted in pancreatic/cholangiocarcinoma tumor bearing nude mice. Molecular and cellular alterations were analyzed in the PEM-implanted pancreatic/cholangiocarcinoma xenograft tumors by Western blot, immunoprecipitation, and immunofluorescence. The quantities of paclitaxel released into the tumor and plasma were determined by liquid chromatography-tandem mass spectroscopy. Paclitaxel from the PEM and its diffusion into the tumor inhibited angiogenesis, which involved suppression of mammalian target of rapamycin (mTOR) through regulation of hypoxia inducible factor (HIF-1) and increased apoptosis. Moreover, implantation of the PEM inhibited tumor-stromal interaction-related expression of proteins such as CD44, SPARC, matrix metalloproteinase-2, and vimentin. Local delivery of paclitaxel from a PEM inhibited growth of pancreatic/cholangiocarcinoma tumors in nude mice by suppressing angiogenesis via the mTOR and inducing apoptosis signal pathway.http://dx.doi.org/10.1155/2015/568981 |
| spellingShingle | Sookhee Bang Sung Ill Jang Su Yeon Lee Yi-Yong Baek Jieun Yun Soo Jin Oh Chang Woo Lee Eun Ae Jo Kun Na Sugeun Yang Don Haeng Lee Dong Ki Lee Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug Gastroenterology Research and Practice |
| title | Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug |
| title_full | Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug |
| title_fullStr | Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug |
| title_full_unstemmed | Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug |
| title_short | Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug |
| title_sort | molecular mechanism of local drug delivery with paclitaxel eluting membranes in biliary and pancreatic cancer new application for an old drug |
| url | http://dx.doi.org/10.1155/2015/568981 |
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