Experimental assessment of pro-lymphangiogenic growth factors in the treatment of post-surgical lymphedema following lymphadenectomy
| Autor: | Molly S. Shoichet, Daniel J. Dumont, Dalia Tobbia, John L. Semple, Harold Kim, Amy Baker, Miles G. Johnston |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Pathology medicine.medical_treatment Vascular Endothelial Growth Factor C Urology Breast Neoplasms Angiopoietin-2 03 medical and health sciences Drug Delivery Systems Postoperative Complications 0302 clinical medicine Edema medicine Animals Humans Regeneration Lymphedema Lymphangiogenesis Lymph node Cells Cultured Mastectomy Lymphatic Vessels 030304 developmental biology Medicine(all) 0303 health sciences Sheep business.industry medicine.disease 3. Good health Transplantation medicine.anatomical_structure Lymphatic system Vascular endothelial growth factor C 030220 oncology & carcinogenesis Lymph Node Excision Female Lymphadenectomy Lymph Nodes medicine.symptom business pro-lymphangiogenic growth factors Research Article |
| Zdroj: | Breast Cancer Research : BCR |
| ISSN: | 1465-542X |
| DOI: | 10.1186/bcr2638 |
| Popis: | Introduction: Lymphedema is a frequent consequence of lymph node excision during breast cancer surgery. Current treatment options are limited mainly to external compression therapies to limit edema development. We investigated previously, postsurgical lymphedema in a sheep model following the removal of a single lymph node and determined that autologous lymph node transplantation has the potential to reduce or prevent edema development. In this report, we examine the potential of lymphangiogenic therapy to restore lymphatic function and reduce postsurgical lymphedema. Methods: Lymphangiogenic growth factors (vascular endothelial growth factor C (VEGF-C)) and angiopoietin-2 (ANG-2) were loaded into a gel-based drug delivery system (HAMC; a blend of hyaluronan and methylcellulose). Drug release rates and lymphangiogenic signaling in target endothelial cells were assessed in vitro and vascular permeability biocompatibility tests were examined in vivo. Following, the removal of a single popliteal lymph node, HAMC with the growth factors was injected into the excision site. Six weeks later, lymphatic functionality was assessed by injecting 125Iodine radiolabeled bovine serum albumin (125I-BSA) into prenodal vessels and measuring its recovery in plasma. Circumferential leg measurements were plotted over time and areas under the curves used to quantify edema formation. Results: The growth factors were released over a two-week period in vitro by diffusion from HAMC, with 50% being released in the first 24 hr. The system induced lymphangiogenic signaling in target endothelial cells, while inducing only a minimal inflammatory response in sheep. Removal of the node significantly reduced lymphatic functionality (nodectomy 1.9 ± 0.9, HAMC alone 1.7 ± 0.8) compared with intact groups (3.2 ± 0.7). In contrast, there was no significant difference between the growth factor treatment group (2.3 ± 0.73) and the intact group indicating improved function with the molecular factors. An increase in the number of regenerated lymphatic vessels at treatment sites was observed with fluoroscopy. Groups receiving HAMC plus growth factors displayed significantly reduced edema (107.4 ± 51.3) compared with nontreated groups (nodectomy 219.8 ± 118.7 and HAMC alone 162.6 ± 141). Conclusions: Growth factor therapy has the potential to increase lymphatic function and reduce edema magnitude in an animal model of lymphedema. The application of this concept to lymphedema patients warrants further examination. peerReviewed |
| Databáze: | OpenAIRE |
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