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| 1 | 重组脊髓灰质炎病毒用于治疗复发胶质母细胞瘤(英文)显示文摘Background The prognosis of patients with recurrent World Health Organization(WHO)grade IV malignant glioma is dismal,and there is currently no effective therapy.We conducted a dose-finding and toxicity study in this population of patients,evaluating convection-enhanced,intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera(PVSRIPO).PVSRIPO recognizes the poliovirus receptor CD155,which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment.Methods We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma,confirmed on histopathological testing,with measurable disease(contrast-enhancing tumor of≥1 cm and≤5.5 cm in the greatest dimension).The study evaluated seven doses,ranging between 107 and 1010 50%tissue-culture infectious doses(TCID50),first in a dose-escalation phase and then in a dose-expansion phase.Results From May 2012 through May 2017,a total of 61 patients were enrolled and received a dose of PVSRIPO.Dose level-1(5.0×107TCID50)was identified as the phase 2 dose.One dose-limiting toxic effect was observed;a patient in whom dose level 5(1010TCID50)was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed.To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use,dose level 5 was deescalated to reach the phase 2 dose.In the dose-expansion phase,19%of the patients had a PVSRIPO-related adverse event of grade 3 or higher.Overall survival among the patients who received PVSRIPO reached a plateau of 21%(95%confidence interval,11 to 33)at 24 months that was sustained at 36 months.Conclusions Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential.The survival rate among patients who receivedPVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. | Desjardins A Gromeier M Herndon JE 2nd Beaubier N Bolognesi DP Friedman AH Friedman HS McSherry F Muscat AM Nair S Peters KB Randazzo D Sampson JH Vlahovic G Harrison WT McLendon RE Ashley D Bigner DD | 2018 | 中华神经外科疾病研究杂志2018，17，4： | 2 |
| 2 | Comprehensive genomic characterization defines human glioblastoma genes and core pathways显示文摘 | Mclendon R Friedman A Bigner D | 2008 | Nature2008，455，7216： | 1 |
| 3 | Comprehensive genomic characterization defines human glioblas- toma genes and core pathways显示文摘 | R McLendon A Friedman D Bigner EG Van Meir DJ Brat GM Mastrogianakis JJ Olson T Mikkelsen and N Lehman | 2008 | Nature2008，455，： | 1 |
| 4 | EGFRvⅢ as a promising target for antibody-based brain tumor therapy显示文摘 | Kuan CT Wikstrand CJ Bigner DD | 2000 | Brain Tumor Pathol2000，17，2： | 1 |
| 5 | Distinct transcription profiles of primary and secondary glioblastoma subgroups显示文摘 | Bigner SH Humphrey PA Wong AJ | 2006 | Cancer Res2006，66，： | 1 |
| 6 | Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification 显示文摘 | Wong AJ Bigner SH Bigner DD | 1987 | Proc Natl Acad Sci U S A1987，84，19： | 1 |
| 7 | Structural alterations of the epidermal growth factor receptor gene in human gliomas显示文摘 | Wong A J Ruppert JM Bigner SH | 1992 | Proc Natl Acad Sci USA1992，89，7： | 1 |
| 8 | EGF mutant receptor will as a molecular target in cancer therapy显示文摘 | Kuan CT Wikstrand CJ Bigner DD | 2001 | Endoct Relat Cancer2001，8，： | 1 |
| 9 | Deletion of p16 and p15 genes in brain tumors显示文摘 | Jen J Itarper JW Bigner SH | 1994 | Cancer Res1994，54，24： | 1 |
| 10 | The role of the subependymal plate in glial tumorigenesis显示文摘 | Vick N A Lin M J Bigner D D | 1977 | Acta Neuropathol(Bed)1977，40，1： | 1 |
| 11 | A novel recombinant immunotoxin- based therapy targeting wild-type and mutant EGFR improves sur- vival in marine models of glioblastoma 显示文摘 | Chandramohan V Bigner DD | 2013 | Oncolmmunology2013，2，26： | 1 |
| 12 | Deletion of p16and p15genes in braintumors显示文摘 | Jen J Harper JW Bigner SH | 1994 | Cancer Res1994，54，24： | 1 |
| 13 | PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer 显示文摘 | Li J Yen C Liaw D Podsypanina K Bose S Wang SI Puc J Miliaresis C Rodgers L McCombie R Bigner SH Giovanella BC Ittmann l Tycko B Hibshoosh H Wigler MH Parsons R | 1997 | Science1997，275，： | 1 |
| 14 | Bispecific antibodies engage T cells for antitumor immunotherapy显示文摘 | Choi B Cai M Bigner D | | 0，，07： | 1 |
| 15 | Identification of an amplified, highly expressed gene in a human glioma 显示文摘 | KW Kinzler SH Bigner DD igner | 1987 | Science1987，236，4797： | 1 |
| 16 | Comprehensive genomic characterization defines human glioblastoma genes and core pathways显示文摘 | MCLENDON R FRIEDMAN A BIGNER D | 2008 | Nature2008，455，7216： | 1 |
| 17 | Comprehensive genomic characterization defines human glioblastoma genes and core pathways显示文摘 | MCLENDON R FRIEDMAN A BIGNER D | 2008 | Nature2008，455，7216： | 1 |
| 18 | Microdosimetry of Alpha-particle-emitting 211 At-labeled Monoclonal Antibody(MAb) Using Histological Images of Malignant Brain Tumors 显示文摘 | Akabani G McLendon RE Bigner DD | 2000 | J Nucl Med2000，84，： | 1 |
| 19 | Radioimmunotherapy with alpha-particle emitting radioimmunoconjugates显示文摘 | Zalutsky MR Bigner DD | | 0，，03： | 1 |
| 20 | Identification of an am- pfified, highly expressed gene in a human glioma显示文摘 | Kinzler KW Bigner SH Bigner DD | 1987 | Science1987，236，4794： | 1 |
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