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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 | In vitro selection and evolution of functional proteins by using ribosome display显示文摘 | Hanes J Plückthun A | 1997 | Proc Natl Acad Sci USA1997，94，10： | 1 |
| 3 | Propofol attenuates hydrogen peroxide-induced mechanical and metabolic derangements in the isolated rat hearts显示文摘 | Hane A | 1996 | Anesthesiology1996，84，1： | 1 |
| 4 | Sequencing inputs to multi-commodity pipelines显示文摘 | Christopher A Hane | 1995 | Annals of Operation Research1995，57，4： | 1 |
| 5 | In vitro selection and evolution of functional proteins by using ribosome display 显示文摘 | Hanes J Pluckthun A | 1997 | Proc Natl Acad Sci USA1997，94，： | 1 |
| 6 | In vitro selection and evolution of functional proteins by using ribosome display显示文摘 | Plückthun A | 1997 | Proc Natl Acad Sci USA1997，94，： | 1 |
| 7 | The tissue renin-angiotensin-aldosterone system in diabetes mellitus显示文摘 | Hanes D S Nahar A Weir M R | 2004 | Cruu Hypertens Rep2004，6，2： | 1 |
| 8 | Large porous particles for pulmonary drug delivery显示文摘 | David A Edwards Justin Hanes | 1997 | Science1997，276，5320： | 1 |
| 9 | In vitro selection and evolution of functional proteins by using roblsome display显示文摘 | Hanes J Pluckthun A | 1997 | Proc Natl Acad Sci USA1997，94，： | 1 |
| 10 | In vitro selection and evolution of functional proteins by using ribosome display 显示文摘 | Hanes J Pluckthun A | 1997 | Proc Nail Acad Sci USA1997，94，10： | 1 |
| 11 | Effectiveness of a strategy to improve adherence to tuberculosis treatment in a resource-poor setting: a cluster randomized controlled trial 显示文摘 | Thiam S Le Fevre A M Hane F | 2007 | JAMA2007，297，40： | 1 |
| 12 | Improving a templated-based classifier in a SAR automatic target recognition system by using 3-D target information 显示文摘 | Verbout S M Irving W W Hanes A S | 1993 | Lincoln Laboratory Journal1993，6，1： | 1 |
| 13 | Evaluation of the prognostic value of IFN-gamma release assay and tuberculin skin test in household contacts of infectious tuberculosis cases in Senegal 显示文摘 | Lienhardt C Fielding K Hane AA Niang A Ndao CT Karam F Fletcher H Mbow F Oomis JF Diadhiou R Toupane M Dieye T Mboup S | 2010 | PLoS One2010，5，10： | 1 |
| 14 | Picomolar affinity anti- bodies from a fully synthetic naive library selected and evolved by ribosome display显示文摘 | Hanes J Schaffitzel C Knappik A | 2000 | Nat Biotechnol2000，18，12： | 1 |
| 15 | Tuberculosis and diabetes显示文摘 | Toure NO Dia Kane Y Diatta A Ba Diop S Niang H Ndiaye EM Thiam K Mbaye FB Hane AA | 2007 | Rev Mal Respir2007，24，7： | 1 |
| 16 | The fleet assignment problem 显示文摘 | Hane C A Barnhart C | 1989 | Interfaces1989，19，4： | 1 |
| 17 | A method for deter- mining the spring constant of cantilevers for atomic force microscopy 显示文摘 | TORII A SASAKI M HANE K | 1996 | Measurement Science and Technology1996，7，2： | 1 |
| 18 | In vitro selection and evolution of functional proteins by using ribosome display显示文摘 | HANES J PLUCKTHUN A | | 0，，： | 1 |
| 19 | Picomolar affinity antibodies from a fully synthetic naive library selected and evolved by ribosome display显示文摘 | Schaffitzel C Knappik A | 2000 | Nat Biotechnol2000，18，： | 1 |
| 20 | Using Branch-and-Price-and-Cut to solve origin-destination integer multi-commodity flow problems显示文摘 | Barnhart C Hane C A Vance P H | 2000 | Opns Res2000，48，2： | 1 |
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