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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 | Inhibition of corneal neo-vascularization by subconjunctival injection of Fc-Endosta-tin,a novel inhibitor of angiogenesis 显示文摘 | YOSfflDA J WICKS RT ZAMBRANO Al TYLER BM JAVA-HERIAN K GROSSMAN R | 2015 | J Ophthalmol2015，2015，13： | 1 |
| 3 | Local delivery of mitoxantronefor the treatment of malignant brain tumors in rats 显示文摘 | DiMeco F Li KW Tyler BM | 2002 | J Neuro- surg2002，97，5： | 1 |
| 4 | Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs 显示文摘 | GUARNIERI M TYLER BM DETOLLA L | 2014 | J Pharm Bioallied Sci2014，6，1： | 1 |
| 5 | Efficient disruption and replacement of an effector gene in the oomycete Phytophthora sojae using CRISPR/Cas9 显示文摘 | Fang Y Tyler BM | 2016 | Mol Plant Pathol2016，17，1： | 1 |
| 6 | Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature显示文摘 | Sills AKJ Williams JI Tyler BM | 1998 | Cancer Res1998，58，： | 1 |
| 7 | Phytophthora genome sequences uncover evolutionary origins and mechanisms of pathogenesis显示文摘 | Tyler BM Tripathy S Zhang X et at | 2006 | Science2006，313，： | 1 |
| 8 | Effect of IgA protease on the ability of secretory IgAl antibodies to inhibit the adherence of streptococcus mutans显示文摘 | Tyler BM Cole M | 1998 | Microbiol Immunol1998，42，7： | 1 |
| 9 | Inhibition of Akt inhib- its growth of glioblastoma and glioblastoma stem - like ceils 显示文摘 | Gallia GL Tyler BM Hann CL | 2009 | nol Cancer Ther2009，8，2： | 1 |
| 10 | Effect of IgA pretease on the ability of secretory IgA antibodies to inhibit the adberence of streptucoccus mutans显示文摘 | Tyler BM Cole M | 1998 | Microbiol Immunol1998，42，7： | 1 |
| 11 | Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature显示文摘 | Sills AK Jr Willams jI Tyler BM | 1998 | Cancer Res1998，58，13： | 1 |
| 12 | Squalamine inhibits angiogensis and solid tumor growth in vivo and perturbs embryonic vasculature显示文摘 | Williams JI Tyler BM | 1998 | Cancer Res1998，58，13： | 1 |
| 13 | Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature 显示文摘 | Sills AK Williams JI Tyler BM Epstein DS Sipos EP Davis JD | 1998 | Cancer Res1998，58，13： | 1 |
| 14 | Local ampullary resection with careful intraoperative frozen section evolution for presumed benign ampullary neoplasms 显示文摘 | Clary BM Tyler DS Dematos P | 2000 | Surg2000，127，6： | 1 |
| 15 | Local ampullary resection with careful intraoperative frozen section evaluation for presumed benign ampullary neoplasms显示文摘 | Tyler DS Dematos P | 2000 | Surgery2000，127，6： | 1 |
| 16 | Establishment of ahuman glioblastoma stemlike brainstem rodent tumormodel显示文摘 | Siu IM Tyler BM Chen JX | 2010 | J Neurosurg Pediatr2010，6，1： | 1 |
| 17 | Multipulse drug delivery from a resorbable polymeric microehip device 显示文摘 | R/CHARDS GRAYSON AC CHOI IS TYLER BM | 2003 | Nat Mater2003，2，11： | 1 |
| 18 | Polilactofate microspheres for Paclitaxel delivery to central nervous system malignancies显示文摘 | LI KW DANG W TYLER BM | 2003 | Clin Cancer Res2003，9，9： | 1 |
| 19 | Local delivery of mitoxantron for the treatment of malignant brain tumors in rats显示文摘 | Dimeco F Li KW Tyler BM | 2002 | J Neurosurg2002，97，5： | 1 |
| 20 | In vitro binding and CNS effects of novel neurotensin agonists that cross the blood-brain barrier显示文摘 | Tyler BM Douglas CL Fauq A | 1999 | Nenropharmacology1999，38，7： | 1 |
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