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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 | CTLA-4(CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression显示文摘 | Carreno BM Bennett F Chau TA | 2000 | J Immunol2000，165，3： | 1 |
| 3 | Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct显示文摘 | Nudo RJ Wise BM SiFuentes F | 1996 | Science1996，272，： | 1 |
| 4 | Surgical treatment of lumbar spinal stenosis:Five-year follow-up显示文摘 | Jolles BM Porchet F Theumann N | 2001 | J Bone Joint Surg Br2001，83，7： | 1 |
| 5 | A protocol for managing severe preeclampsia in the second trimester显示文摘 | Sibai BM Akl S Fairlie F | 1990 | Am J Obstet Gynecol1990，163，3： | 1 |
| 6 | Chemoradiation instead of surgery to treat mid and low rectal tumors: is it safe? 显示文摘 | Nakagawa WT Rossi BM de O Ferreira F | 2002 | Ann Surg Oncol2002，9，6： | 1 |
| 7 | Phytoayailability and toxiciW of trivalent and hexavalent chromium to brassica juncea显示文摘 | Han F X SridharB BM MontsD L | 2004 | New Phytologist2004，162，2： | 1 |
| 8 | Fish welfare and quality as affected by pre-slaughter and slaughter management显示文摘 | POLI BM PARISI G SCAPPINI F | 2005 | Aquaculture International2005，，13： | 1 |
| 9 | Effects of two years of daily teriparatide treatment on bone mineral density in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment显示文摘 | Obermayer-Pietsch BM Marin F Mc Closky EV | 2008 | J Bone Miner Res2008，，10： | 1 |
| 10 | Isolation and characterization of porcine circovirus 2 from cases of sow abortion and porcine dermatitis and nephropathy syndrome 显示文摘 | Meehan BM McNeilly F McNair I Walker I Ellis JA Krakowka S Allan GM | 2001 | Arch Virol2001，146，4： | 1 |
| 11 | Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence 显示文摘 | Hsu DW Hakim F Biller BM | 1993 | J Neurosurg1993，78，5： | 1 |
| 12 | Hepatoctye transplantation in acute liver failure 显示文摘 | Bilir BM Guenette D Karrer F | 2000 | Liver Transpl2000，6，1： | 1 |
| 13 | Diagnosis of Hymenoptera venom allergy显示文摘 | Bilo BM Rueff F Mosbech H | 2005 | Allergy2005，60，11： | 1 |
| 14 | Neural substrates for the effects of rehabilatative training on motor recovery following ischemic infarct显示文摘 | Nudo RJ Wise BM SiFuentes F | 1996 | Science1996，272，5269： | 1 |
| 15 | Repair of ful-thickness femoral condyle cartilage defects using al ogeneic synovial cel-engineered tissue constructs显示文摘 | Pei M He F Boyce BM | | 0，，06： | 1 |
| 16 | Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases显示文摘 | Papasotiriou M Genovese F Klinkhammer BM | 2015 | Nephrol Dial Transplant2015，16，： | 1 |
| 17 | PTEN regulates p300-dependent hypoxia-inducible factor 1 transcriptional activity through Forkhead transcription factor 3a (FOXO3a) 显示文摘 | Emerling BM Weinberg F Liu JL | 2008 | Proc NatlAcadSciUSA2008，105，7： | 1 |
| 18 | High-pressure methane and carbon dioxide adsorption on dry and moisture-equilibrate pennsylvanian coals显示文摘 | Kross BM van Bergen F Gensterblum Y | 2002 | International Journal of Coal Geology2002，51，： | 1 |
| 19 | Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct显示文摘 | Wise BM SiFuentes F | 1996 | Science1996，272，： | 1 |
| 20 | Performance of commercial blood tests for the diagnosis of latent tuberculosis infection in children and adolescents 显示文摘 | Bergamini BM Losi M Vaienti F | 2009 | Pediatrics2009，123，： | 1 |
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