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多形性胶质母细胞瘤 1

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胶质瘤干细胞 1

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Long acting carmustine loaded natural extracellular matrix hydrogel for inhibition of glioblastoma recurrence

《化学科学与工程前沿（英文）》 2022年第16卷第4期页码 536-545 doi: 10.1007/s11705-021-2067-5

摘要： Many scientific efforts have been made to penetrate the blood-brain barrier and target glioblastoma cells, but the outcomes have been limited. More attention should be given to local inhibition of recurrence after glioblastoma resection to meet real medical needs. A biodegradable wafer containing the chemotherapeutics carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU) was the only local drug delivery system approved for clinical glioblastoma treatment, but with a prolonged survival time of only two months and frequent side effects. In this study, to improve the sustained release and prolonged therapeutic effect of drugs for inhibiting tumor recurrence after tumor resection, both free BCNU and BCNU- poly (lactic-co-glycolic acid) (the ratio of lactic acid groups to glycolic acid groups is 75/25) nanoparticles were simultaneously loaded into natural extracellular matrix hydrogel from pigskin to prepare BCNU gels. The hydrogel was injected into the resection cavity of a glioblastoma tumor immediately after tumor removal in a fully characterized resection rat model. Free drugs were released instantly to kill the residual tumor cells, while drugs in nanoparticles were continuously released to achieve a continuous and effective inhibition of the residual tumor cells for 30 days. These combined actions effectively restricted tumor growth in rats. Thus, this strategy of local drug implantation and delivery may provide a reliable method to inhibit the recurrence of glioblastoma after tumor resection in vivo.

关键词： BCNU glioblastoma recurrence tumor resection nanoparticles hydrogel

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A reignited debate over the cell(s) of origin for glioblastoma and its clinical implications

Xiaolin Fan, Yanzhen Xiong, Yuan Wang

《医学前沿（英文）》 2019年第13卷第5期页码 531-539 doi: 10.1007/s11684-019-0700-1

摘要： Glioblastoma (GBM) is the most common and lethal primary neoplasm in the central nervous system. Despite intensive treatment, the prognosis for patients with GBM remains poor, with a median survival of 14−16 months. 90% of GBMs are primary GBMs that are full-blown at diagnosis without evidences of a pre-existing less-malignant precursor lesion. Therefore, identification of the cell(s) of origin for GBM—the normal cell or cell type that acquires the initial GBM-promoting genetic hit(s)—is the key to the understanding of the disease etiology and the development of novel therapies. Neural stem cells and oligodendrocyte precursor cells are the two major candidates for the cell(s) of origin for GBM. Latest data from human samples have reignited the longstanding debate over which cells are the clinically more relevant origin for GBMs. By critically analyzing evidences for or against the candidacy of each cell type, we highlight the most recent progress and debate in the field, explore the clinical implications, and propose future directions toward early diagnosis and preventive treatment of GBMs.

关键词： glioblastoma cell(s) of origin neural stem cells oligodendrocyte precursor cells subventricular zone early diagnosis

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硼中子俘获治疗人脑胶质母细胞瘤的前景和困惑

周幽心,孙婷,杨伟廉,杜子威

《中国工程科学》 2012年第14卷第8期页码 82-84

摘要：

硼中子俘获疗法是一种可以选择性杀伤肿瘤细胞的放射疗法，其产生的α粒子对临床治疗新诊断和复发的脑胶质母细胞瘤有较好的疗效。发达国家20世纪五六十年代就已进入临床试验，但一直受到硼携带载体和中子源发展的限制。现就其治疗脑胶质母细胞瘤的前景做一综述。

关键词：硼中子俘获疗法多形性胶质母细胞瘤胶质瘤干细胞

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¹³¹I标记的人源化抗B7-H3抗体用于胶质母细胞瘤放射免疫疗法的治疗特性 Article

傅丰庆, Meng Zheng, Shandong Zhao, Yan Wang, Minzhou Huang, Hanqing Chen, Ziyi Huang, Kaijie Zhang, 缪丽燕, 张学光

《工程（英文）》 2023年第30卷第11期页码 190-202 doi: 10.1016/j.eng.2023.05.011

摘要：

B7 homolog 3 (B7-H3) has attracted much attention in glioblastoma (GBM) radioimmunotherapy (RIT) due to its abnormally high expression on tumor cells. In this study, we report that two specific humanized anti-human B7-H3 antibodies (hu4G4 and hu4H12) derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells. Hu4G4 and hu4H12 were radiolabeled with ⁸⁹Zr for RIT antibody screening. Micro-positron emission tomography (PET) imaging, biodistribution and pharmacokinetic (PK) analyses of ⁸⁹Zr-labeled antibodies were performed in U87-xenografted models. ¹²⁵I labelling of the antibodies for single-photon emission computed tomography (SPECT) imaging was also used to investigate the biological behavior of the antibodies in vivo. Furthermore, the pharmacodynamic (PD) of the 131Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models. Micro-PET imaging and biodistribution analysis with a gamma counter showed that ⁸⁹Zr-deferoxamine (DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than ⁸⁹Zr-DFO (hu4H12, immunoglobulin G (IgG)). The biodistribution results of ¹²⁵I-SPECT imaging were similar to those of ⁸⁹Zr-PET imaging, though the biodistribution in long bone joints and the thyroid varied. The PD analysis results indicated that 131I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity. Interestingly, 131I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen type IV and platelet-derived growth factor receptor b (PDGFR-b) compared with control treatment, as determined by immunofluorescence (IF), which contributed to inhibiting tumor growth. Taken together, our data indicate that hu4G4 exhibits good tumor targeting and specificity, achieves low nonspecific concentrations in normal tissues, and has acceptable PK characteristics. 131I-hu4G4 also exerts effective antitumor effects with an ideal safety profile. Therefore, we expect hu4G4 to be an excellent antibody for the development of GBM RIT.

关键词： B7-H3 Radioimmunotherapy Glioblastoma Pharmacokinetics Pharmacodynamics