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| 1 | Local immunotherapy with interleuk in-2 delivered from biodegradable p olymer microspheres combined with interstitial chemotherapy:a novel treatme nt for experimental malignant glioma显示文摘OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradable polymers prolon gs survival against experimental brain tumors.Moreover,paracrine administration of inte rleukin-2(IL-2)has been shown to elicit a potent antitumor immune response and to improve survival in animal brain tumor models.We r eport the use of a novel polymeric mic rosphere delivery vehicle to release IL-2.We demonstr ate both in vitro release of cytokine from the microspheres and histological evidence of the inflammatory response elicited by I L-2released from the microspheres i n the rat brain.These microspheres a re used to deliver IL-2,and biodegradable polymer wafers are used to deliver BCNU,directly at the site of an intracranially implanted glioma in the rat.The two agents administered locally show a s ynergistic effect.METHODS:Fischer 344rats challenged intracranially with 9L gliosarcoma received an intracranial implant of either empty microspheres or microspheres containing IL-2(IL-2MS ).Five days later,animals in each group were randomized to receiv e polymer implants loaded with 0,3.8,or 10%BCNU at the tumor site.RESULTS:Animals that received the combination of IL-2MS a nd 3.8%BCNU polymer(median survival,28.5d )or IL-2MS and 10%BCNU polymer(median survival,45.5d )showed significantly improved surv ival compared with animals that rece ived monotherapy with IL-2microsph eres(median survival,24d ),3.8%BCNU polymer(median survival,24d ),or 10%BCNU polymer(median survival,32.5d ).Control animals had a median survival of 18days.The combination of either 3.8or 10%BCNU polymer with IL-2MS resulted in 7and 25%long-term survivors,respectively.CONCLUSION:By showing synergy of IL-2and BCNU in an animal glioma model and using a reproducible synthetic delivery sy stem for each agent (i.e.,one that did not rely on genetic ally engineered cells or viruses),we hope that the combination of local immunotherapy and chemotherapy can take an important step closer to clinical applic ation in patients with malignant brain | Rhines LD DiMeco F Lawson HC Tyler BM Hanes J Olivi A Brem H | 2003 | 癌症2003，22，7： | 2 |
| 2 | A six-component yield function for anisotropic metals显示文摘 | Lege D J Brem J C | 1991 | Inernational Journal of Plasticity1991，427，13： | 1 |
| 3 | A six-component yield function for anisotropic materials显示文摘 | BARLAT F LEGE D J BREM J C | | 0，，07： | 1 |
| 4 | Treatment of murine hemangioendotheliomas with the angiogenesis inhibitor AGM-1470 显示文摘 | O' Reilly M Brem H Folkman J | 1995 | J Pediatr Surg1995，30，2： | 1 |
| 5 | Evidence- based protocol for diabetic foot ulcers 显示文摘 | Brem H Sheehan P Rosenberg H J | 2006 | Plast Reconstr Surg2006，117，7： | 1 |
| 6 | Evidence - based protocol for diabetic foot ulcers 显示文摘 | Brem H Sheehan P Rosenberg H J | 2006 | Plast Reconstr Surg2006，，： | 1 |
| 7 | A six-component yield function for anisotropic materials显示文摘 | BARLAT F LEGE D J BREM J C | 1991 | Int J Plasticity1991，7，： | 1 |
| 8 | Plane stress yield function for aluminum alloy sheets-part h Theory显示文摘 | BARLAT F BREM J C YOON J W | | 0，，： | 1 |
| 9 | Yielding description of solution strengthened aluminium alloys显示文摘 | BARLAT F BECKER R C HAYASHIDA Y MAEDA Y YANAGAWA M CHUNG K BREM J C LEGE D J MATSUI K MURTHA S J HATTORI S | 1997 | Int J Plasticity1997，13，： | 1 |
| 10 | Prolonged tumor dormancy by prevention of neovascularization in the vitreous显示文摘 | Brem S Brem H Folkman J | 1976 | Cancer Res1976，36，8： | 1 |
| 11 | Yield function development for aluminium alloy sheets显示文摘 | BARLAT F MAEDA Y CHUNG K YANAGAWA M BREM J C HAYASHIDA Y LEGE D J MATDUI K MURTHA S J HATTORI S BECKER R C MAKOSEY S | 1997 | J Mech Phys Solids1997，45，1112： | 1 |
| 12 | In Vivo Versus in vitro Degradation of Controlled Release Polymers for Intracranial Surgical Therapy显示文摘 | Wu M P Tamada J A Brem H | 1994 | J Biomed Mater Res1994，28，： | 1 |
| 13 | A six-component yield function for anisotropic materials显示文摘 | BARLAT F LEGE D J BREM J C | 1991 | International Journal of Plasticity1991，7，7： | 1 |
| 14 | Plane stress yield function for aluminum alloy sheets (Part I):Theory显示文摘 | BARLAT F BREM J C YOON J W CHUNG K DICK R E LEGE D J POURBOGHRAT F CHOI S H CHU E | 2003 | Int J Plasticity2003，19，： | 1 |
| 15 | Lipase mediated sequential resolution of aromatic β-hydroxy esters using fatty acid derivatives 显示文摘 | Brem J Naghi M Tosa MI | 2011 | Tetrahedron: Asymmetry2011，22，1617： | 1 |
| 16 | Potentiation of anticancer effects of microencapsulated carboplatin by hydroxypropyla-cyclodextrin显示文摘 | Utsuki T Brem H Pitha J | 1996 | J Controlled Release1996，40，： | 1 |
| 17 | Evaluation and management of valgus impacted four - part proximal humerus fractures 显示文摘 | DeFranco M J Brems JJ Williams GR Jr | 2006 | Clin Orthop Relat Res2006，，442： | 1 |
| 18 | Evidence-Based Protocol for Diabetic Foot Ulcers显示文摘 | Harold Brem MD Peter Sheehan MD Harvey J | 2006 | Plast Reconstr Surg2006，，： | 1 |
| 19 | The glenoid component in total shoulder arthroplasty显示文摘 | Brem J | 1993 | J Shoulder Elbow Surg1993，2，： | 1 |
| 20 | BEM- models for the propa- gation period of chloride induced reinforcement corrosion显示文摘 | WARKUS J BREM M RAUPACH M | 2006 | Mate- rials and Corrosion2006，57，8： | 1 |
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