Phase II Trial O6-benzylguanine(BG) and Temozolomide(TMZ) Therapy of Glioblastoma Multiforme (GBM) With Infusion of Autologous P140K MGMT+Hematopoietic Progenitors to Protect Hematopoiesis

This phase II trial studies the effect of P140K MGMT hematopoietic stem cells, O6-benzylguanine, temozolomide, and carmustine in treating participants with supratentorial glioblastoma or gliosarcoma who have recently had surgery to remove most or all of the brain tumor (resected). Chemotherapy drugs, such as 6-benzylguanine, temozolomide, and carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing. Placing P140K MGMT, a gene that has been created in the laboratory into bone marrow making the bone more resistant to chemotherapy, allowing intra-patient dose escalation which kills more tumor cells while allowing bone marrow to survive.

开始日期2023-01-20

申办/合作机构

The Case Comprehensive Cancer Center

[+1]

NCT02343666

/ Withdrawn临床1期IIT

A Clinical Trial of Gene-Modified Stem Cells to Generate HIV-Resistant Cells in Conjunction With Standard Chemotherapy for Treatment of Lymphoma in Patients With HIV Infection

This pilot phase I trial studies the side effects and best dose of human immunodeficiency virus (HIV)-resistant gene modified stem cells in treating HIV-positive patients who are undergoing first-line treatment for Hodgkin or Non-Hodgkin Lymphoma. Stem cells are collected from the patient and HIV-resistance genes are placed into the stem cells. The stem cells are then re-infused into the patient. These genetically modified stem cells may help the body make cells that are resistant to HIV infection.

开始日期2016-08-15

申办/合作机构

Fred Hutchinson Cancer Research Center

[+2]

NCT01769911

/ WithdrawnN/AIIT

AUTOLOGOUS TRANSPLANTATION AND STEM CELL BASED-GENE THERAPY FOR THE TREATMENT OF HIV-ASSOCIATED LYMPHOMA

This clinical trial studies genetically modified peripheral blood stem cell transplant in treating patients with HIV-associated non-Hodgkin or Hodgkin lymphoma. Giving chemotherapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. Laboratory-treated stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy

开始日期2015-02-01

申办/合作机构

Fred Hutchinson Cancer Research Center

[+1]

100 项与苄基鸟嘌呤相关的临床结果

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100 项与苄基鸟嘌呤相关的转化医学

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100 项与苄基鸟嘌呤相关的专利（医药）

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198

项与苄基鸟嘌呤相关的文献（医药）

2024-11-01·3 Biotech

Enhancing glioblastoma cytotoxicity through encapsulating O6-benzylguanine and temozolomide in PEGylated liposomal nanocarrier: an in vitro study

Article

作者: Goda, Jayant Sastri ; Rao, B S Satish ; Mutalik, Srinivas ; Rao, B. S. Satish ; Mutalik, Sadhana P. ; Hegde, Manasa Manjunath ; Palkar, Pranoti ; Mutalik, Sadhana P

Abstract:

Glioblastoma (GBM) (grade IV glioma) is the most fatal brain tumor, with a median survival of just 14 months despite current treatments. Temozolomide (TMZ), an alkylating agent used with radiation, faces challenges such as systemic toxicity, poor absorption, and drug resistance. To enhance TMZ effectiveness, we developed poly(ethylene glycol) (PEG) liposomes co-loaded with TMZ and O6-benzylguanine (O6-BG) for targeted glioma therapy. These liposomes, prepared using the thin-layer hydration method, had an average size of 146.33 ± 6.75 nm and a negative zeta potential (−49.6 ± 3.1 mV). Drug release was slower at physiological pH, with 66.84 ± 4.62% of TMZ and 69.70 ± 2.88% of O6-BG released, indicating stability at physiological conditions. The liposomes showed significantly higher cellular uptake (p < 0.05) than the free dye. The dual drug-loaded liposomes exhibited superior cytotoxicity against U87 glioma cells, with a lower IC50 value (3.99µg/mL) than the free drug combination, demonstrating enhanced anticancer efficacy. The liposome formulation induced higher apoptosis (19.42 ± 3.5%) by causing sub-G0/G1 cell cycle arrest. The novelty of our study lies in co-encapsulating TMZ and O6-BG within PEGylated liposomes, effectively overcoming drug resistance and improving targeted delivery for glioma treatment.

2023-11-01·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Development and in vitro evaluation of carmustine delivery platform: A hypoxia-sensitive anti-drug resistant nanomicelle with BBB penetrating ability

Article

作者: Ren, Ting ; Xiao, Zhixuan ; Li, Duo ; Zhong, Rugang ; Zhao, Lijiao ; Wang, Xiaoli ; Sun, Guohui ; Zhang, Na

Glioma is extremely difficult to be completely excised by surgery due to its invasive nature. Thus, chemotherapy still is the mainstay in the treatment of glioma after surgery. However, the natural blood-brain barrier (BBB) greatly restricts the penetration of chemotherapeutic agents into the central nervous system. As a front-line anti-glioma agent in clinical, carmustine (BCNU) exerts antitumor effect by inducing DNA damage at the O⁶ position of guanine. However, the therapeutic effect of BCNU was largely decreased because of the drug resistance mediated by O⁶-alkylguanine-DNA alkyltransferase (AGT) and insufficient local drug concentrations. To overcome these obstacles, we synthesized a BCNU-loaded hypoxia-responsive nano-micelle with BBB penetrating capacity and AGT inhibitory activity, named as T80-HA-AZO-BG/BCNU NPs. In this nano-system, Tween 80 (T80) serves as a functional coating on the surface of the micelle, promoting transportation across the BBB. Hyaluronic acid (HA) with active tumor-targeting capability was linked with the hydrophobic O⁶-benzylguanine (BG) analog via a hypoxia-sensitive azo bond. Under hypoxic tumor microenvironment, the azo bond selectively breaks to release O⁶-BG as AGT inhibitor and BCNU as DNA alkylating agent. The synthesized T80-HA-AZO-BG/BCNU NPs showed good stability, favorable biocompatibility and hypoxia-responsive drug-releasing ability. T80 modification improved the transportation of the micelle across an in vitro BBB model. Moreover, T80-HA-AZO-BG/BCNU NPs exhibited significantly enhanced cytotoxicity against glioma cell lines with high AGT expression compared with traditional combined medication of BCNU plus O⁶-BG. We expect that the tumor-targeting nano-micelle designed for chloroethylnitrosourea will provide new tools for the development of effective glioma therapy.

2023-07-01·Journal of controlled release : official journal of the Controlled Release Society

Yeast cell membrane-camouflaged PLGA nanoparticle platform for enhanced cancer therapy.

Article

作者: Qin, Si-Yong ; Cheng, Yin-Jia ; He, Yu ; Chen, Qi-Wen ; Zhang, Ai-Qing ; Liu, Wen-Long ; Yu, Jin-Xin ; Zhang, Xian-Zheng ; Ma, Yi-Han ; Chen, Xiao-Sui

Temozolomide (TMZ) is an oral DNA-alkylating drug used in colorectal cancer (CRC) chemotherapy. In this work, we proposed a safe and biomimetic platform for macrophages-targeted delivery of TMZ and O⁶-benzylguanine (O⁶-BG). TMZ was loaded in poly (D, l-lactide-coglycolide) (PLGA) nanoparticles, followed by sequential coating with O⁶-BG-grafted chitosan (BG-CS) layers and yeast shell walls (YSW) via layer-by-layer assembly (LBL) process, forming TMZ@P-BG/YSW biohybrids. Due to the yeast cell membrane-camouflage, TMZ@P-BG/YSW particles exhibited significantly enhanced colloidal stability as well as low premature drug leakage in simulated gastrointestinal conditions. In vitro drug release profiles of TMZ@P-BG/YSW particles revealed noticeable higher TMZ release in simulated tumor acidic environment within 72 h. Meanwhile, O⁶-BG could down-regulate MGMT expression in CT26 colon carcinoma cells, ultimately facilitating TMZ-induced tumor cell death. After oral delivery of yeast cell membrane-camouflaged particles containing fluorescent tracer (Cy5), TMZ@P-BG/YSW and bare YSW displayed high retention time of 12 h in the colon and small intestine (ileum). Correspondingly, oral gavage administration of TMZ@P-BG/YSW particles afforded favorable tumor-specific retention and superior tumor growth inhibition. Overall, TMZ@P-BG/YSW is validated to be a safe, targetable and effective formulation, paving a new avenue towards highly effective and precise treatment of malignancies.

项与苄基鸟嘌呤相关的新闻（医药）

2024-12-11

·CPHI制药在线

酵母微胶囊技术的研究应用进展

关注并星标CPHI制药在线微囊化是一种固定化技术，其通过提供一个物理屏障克服外界环境对包封分子的影响，从而提高包合物的稳定性。酵母是一类单细胞真菌，酵母及其生物制剂已经广泛应用在食品工业、生物医药等领域。酵母微囊从酵母中提取，其成分主要是 β-葡聚糖，形状呈椭圆形，具有约2-5 μm 的中空多孔结构。β-葡聚糖是酵母细胞壁的主要结构成分，在结构上主要由 β-1,3-葡聚糖的主链和β-1,6-葡聚糖的侧链组成，其单糖组成为葡萄糖。其中 β-1,3-葡聚糖既构成了葡萄糖刚性网络结构，也为酵母微囊提供了免疫活性。β-1,3-葡聚糖是真菌的主要病原体相关分子模式，它能够被肠道免疫细胞通过多种模式识别受体(包括补体受体 3 和 Dectin-1 受体)识别出来，从而引起相关免疫反应。研究对比多种微生物（如霉菌、原生虫、酵母菌）作为壁材的包埋效果，结果发现采用酵母微胶囊包埋效果最理想。对于所有的包封体系，包封分子与基质之间的相互作用对其稳定性和生物利用度都有着重要的影响。而经酵母包埋后的活性物质稳定性、生物利用度、溶解性和缓释性均有所提高。酵母细胞以分散的单细胞状态存在，其完整的细胞壁和细胞膜结构具有一定的强度和通透性，从而使酵母细胞具有很好的吸附性能，可作为一种新型的微胶囊壁材。酵母细胞有一层磷脂膜，因此它可以充当脂质体，既可以封装疏水化合物，也可以封装亲水化合物。而且酵母微囊由β-葡聚糖构成了一个内部中空、表面多孔且带负电荷的结构，因此大多数的药物都可以在酵母微囊的内部被封装或者吸附在酵母微囊表面，有利于药物的递送。随着研究的不断发展，酵母微囊的药物装载策略逐渐增多，主要包括以下5 种。 (1) 通过静电吸附作用将带正电的药物装载到酵母微囊内部。例如，有学者制备了带有正电荷的顺铂(cisplatin, CDDP)前体纳米粒(PreCDDP)，并将其封装到酵母微囊中，开发了一种安全有效的口服顺铂药物递送平台。此外，通过在酵母微囊表面负载带有相反电荷的胰岛素，并用海藻酸盐进行包被，可成功实现胰岛素的口服递送。 (2) 对于带负电荷的药物，可以通过非共价作用力修饰带正电荷的载体材料，再通过静电吸附作用装载到酵母微囊中。如首先将小檗碱(berberine, BBR)、表没食子儿茶素没食子酸酯(epigallocatechin gallate, EGCG)和 Mn2+通过非共价分子间作用力自组装成纳米颗粒(BBR/MPNNPs)，而后进一步装载到酵母微囊中。将DOX装载在3-巯基丙酸(3-mercaptopropionic acid, MPA)修饰的纳米氧化锌(ZnO NPs)上，构建了带负电荷的载药纳米粒(MPA-ZnO-DOX)，再用聚乙烯亚胺(polyethyleneimine, PEI)将酵母微囊内部修饰成正电荷，使 MPA-ZnO-DOX 能够装载在酵母微囊中。 (3) 可以利用被动扩散或疏水作用将不带电的药物修饰进酵母微囊中。如通过被动扩散将牛血清蛋白(bovine serum albumin, BSA)包封在被壳聚糖包被的酵母微囊里。此外，咖啡因、维生素 B12 等都可以通过相互孵育利用被动扩散装载到酵母微囊中。 (4) 部分药物还可以通过逐层合成(LBL)进行装载。通过静电相互作用将带有相反电荷的多糖依次沉积在预先装载花青素的酵母微囊上，制备出用于花青素包封和稳定的口服递送载体。如将替莫唑胺 (temozolomide,TMZ) 装载在聚乳酸-羟基乙酸共聚物 (poly(lactic-co-glycolic acid), PLGA)中，并通过逐层合成依次包裹 O6-苄基鸟嘌呤(O6-benzylguanine,O6-BG)接枝的壳聚糖(BG-chitosan, BG-CS)层和酵母微囊，最终获得了一个稳定的 TMZ 口服递送平台。 (5) 某些药物还可以将其与衍生化的酵母微囊进行结合。如使用原位合成酵母微囊包覆镍纳米颗粒，将带有His-tag的Cda2 蛋白通过非共价作用力装载进酵母微囊中。使用 NaIO4 对酵母微囊进行氧化，使其具有醛基，进而与卵清蛋白(ovalbumin, OVA)的伯胺基反应，将 OVA 通过化学连接到酵母微囊表面，从而在体内产生有效的特异性免疫反应。酵母微胶囊技术作为口服药物递送系统的研究应用 1、降血糖 Ⅰ型糖尿病是一种与碳水化合物代谢受损相关的代谢紊乱，可导致慢性高血糖，该疾病的特征是β 细胞进行性自身免疫破坏，导致胰岛素不足或胰岛素分泌缺陷。胰岛素皮下注射用于糖尿病的日常治疗。但是由于胰岛素给药带来的不便，很难满足患者的依从性。为了克服这个困难，可优先选择口服胰岛素输送系统。然而，口服胰岛素必须克服某些生理障碍。侵入性和强化方法促使人们需要一种相容的胰岛素给药途径。酿酒酵母的微胶囊可以通过静电力介导的自发沉积结合不同的带电纳米粒子，长期服用酵母微胶囊在治疗慢性疾病方面显示出良好的安全性。有研究首次提出了一种利酵母微胶囊包埋胰岛素抑制糖尿病的生物激励方法。利用胰岛素和酵母微胶囊之间的静电相互作用促使酵母微胶囊包埋胰岛素的形成，并在荧光成像下证实了这一点。在酵母微胶囊包埋胰岛素的表面装载海藻酸钠涂层可以保护酵母微胶囊免受恶劣的胃肠道环境影响，防止胰岛素降解。药理学实验发现，糖尿病大鼠口服海藻酸钠包覆的酵母微胶囊包埋胰岛素后血糖明显降低。 2、治疗心血管疾病心血管疾病的发生和动脉硬化紧密相关。近年来，基于纳米粒子的靶向策略被认为是治疗动脉粥样硬化（AS）的新途径。有学者研发了一种用于靶向治疗心血管疾病的方法，该方法由酵母衍生微胶囊（YC）介导，利用静电驱动自发沉积的方式使不同带电纳米颗粒成功负载到 YC 中。口服给药后，包埋纳米颗粒的酵母胶囊（YDMC）可以优先到达关节炎和肿瘤的病变部位，并显著降低斑块面积，增强 AS 斑块的稳定性。最重要的是，实验发现 YC介导的纳米疗法比未包装的纳米药物更有效，对毒性测定的结果显示包装后的纳米药物在长期口服后表现出良好的安全性，因此该方法或可用于 AS 和其他血管疾病的靶向治疗。单核细胞趋化蛋白 -1（MCP-1）在 AS 中扮演着关键的角色，是 AS 发生早期的重要因素。有学者利用上述YC 介导的仿生方法成功将一种 MCP-1 的特异性合成抑制剂靶向输送到 AS 斑块内部，结果显示这种抑制剂的作用明显增强，有效减少了单核细胞在 AS 斑块中的聚集。 3、治疗炎症相关疾病胃肠道存在许多生物屏障，即使是当前最先进的纳米粒子靶向传递系统口服给药后也面临来自胃肠道障碍的挑战。有学者尝试将含有消炎药吲哚美辛或抗肿瘤药物紫杉醇的纳米粒负载到酵母胶囊中，口服后经过一系列的体内运输过程，包埋在酵母胶囊中的纳米粒最终被传递到小鼠或大鼠炎症或肿瘤的远程病变部位。结果显示，在该急性炎症模型中，酵母胶囊介导的纳米探针的靶向效率甚至比静脉注射相同剂量的纳米探针的靶向效率还要高。口服经酵母胶囊介导的吲哚美辛或紫杉醇纳米疗法在炎症和肿瘤动物模型中与单独纳米治疗相比，作用显著增强。利用酵母细胞包封姜黄素研究其在体外的抗炎作用，发现克服姜黄素生物利用度低、提高靶向传递主要是酵母细胞中纯化的葡聚糖颗粒发挥作用。 4、抗肿瘤口服是最常见和最有效的给药方式，具有较高的安全性、方便性和用药依从性。目前，口服抗肿瘤药物在治疗癌症方面越来越受欢迎。但一些治疗癌症的口服药物存在亲水性低、对上皮细胞渗透性差、毒副作用大等问题。卡巴他赛是一种新型半合成紫杉醇，具有很强的抗肿瘤活性，与其他紫杉醇类似，卡巴他赛的口服给药仍然受到限制，有学者将载药聚合物-脂质杂化纳米粒子（NPs）负载到多孔空心酵母细胞壁微颗粒（YPs）中，制备了一种载药纳米微载体，用于巨噬细胞靶向口服卡巴他赛；在模拟胃肠道环境中，NPs 负载 YPs的体外释药速度较 NPs 慢，药物稳定性较高；体内药动学研究中，卡巴他赛溶液的口服利用度提高了5倍。顺铂是当前联合化疗中最常用的药物之一，将制备好的顺铂衍生的前体纳米粒子（PreCDDP）封装到酵母胶囊中得到可以口服给药的 PreCDDP/YC，并从其理化性质、体外药物释放、体外抗肿瘤活性、口服靶向性、体内药动学和体内药效等方面对酵母胶囊仿生给药系统进行考察，结果 PreCDDP/YC在细胞内释放后仍具有抗肿瘤活性，口服载于酵母胶囊中的 PreCDDP 比口服或静脉注射游离的顺铂具有更好的安全性和更高的生物利用度。上述研究表明载药纳米微载体技术是增加小分子药物口服吸收的一种可能途径。酵母微囊作为口服递送载体具有诸多优势。首先，因为人体胃肠道中缺乏可以降解 β-葡聚糖的酶，而且 β-葡聚糖具有耐酸的特性，所以以 β-葡聚糖为主要成分的酵母微囊可以避免在恶劣的肠道环境中被消化降解，保护药物可以顺利通过复杂的肠道环境而不被破坏。其次， β-葡聚糖是一种来源于酵母细胞的载体，因此可以模仿酵母的行为，被 M 细胞上的 Dectin-1 识别，从而通过复杂的巨噬细胞介导运动，将各种药物准确、安全地靶向地送到病变部位。酵母微囊对极性和非极性的小分子具有良好的渗透性，而且可以通过调节表面紧密连接程度促进对生物大分子的吸收，所以可以有效地装载各类大分子和小分子的药物，例如蛋白质、DNA、抗原、姜黄素等。最后，酵母微囊具有无细胞毒性以及安全的特点，这是作为口服递送载体的一大根本要求。参考资料 [1]李文,刘夫锋.基于益生菌口服药物递送系统的研究进展[J].微生物学报,2024,64(11):4086-4105. [2]贾丽娟,戴智强,高青青,等.酵母微胶囊包埋新技术及药效评价的研究进展[J].中南药学,2022,20(04):871-876. 作者简介：小泥沙，食品科技工作者，食品科学硕士，现就职于国内某大型药物研发公司，从事营养食品的开发与研究。 END 【智药研习社近期直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

2023-05-09

·FierceBiotech

SNAPing together a universal receptor system for T cell therapies

The researchers designed two different types of receptors containing SNAPtag: chimeric antigen receptors and SynNotch receptors, synthetic receptors that can be programmed to turn on or off virtually any gene T cell therapies work well for blood cancers, but they come with caveats—a major one being that they’re cumbersome and expensive to tailor to a patient’s specific cancer type. On top of that, the therapy must be re-customized to home in on a new target each time the cancer evolves. Now, a new universal receptor system designed by a research team from the University of Pittsburgh could make engineering custom T cell therapies far more efficient. Part of the company’s technology has already been licensed by Pennsylvania-based biotech Coeptis Therapeutics. In a study published May 9 in Nature Communications, the scientists described how they engineered T cells with receptors containing a special enzyme called SNAPtag. The engineered cells are administered alongside antibodies for proteins specific to a patient’s cancer. These antibodies are labeled with a molecule called benzylguanine, which forms a covalent bond—the strongest type there is—with SNAPtag. This welds the antibodies to the receptor so it’s able to recognize the cancer cells. “We wanted to make receptors that wouldn’t just bind with the adapter antibodies—it would actually fuse with them,” senior author Jason Lohmueller, Ph.D., told Fierce Biotech Research. “This would allow them to have more potent activity so we could get by with a lower amount of that antibody and get more sensitive responses.” Lohmueller’s lab, together with the lab of Alexander Deiters, Ph.D., also at the University of Pittsburgh, is one of the first to use SNAPtag in a therapeutic setting. Benzylguanine by itself is an antineoplastic agent that’s been used to make tumor cells more vulnerable to cancer drugs. SNAPtag and benzylguanine together have been used in imaging in animals and to label proteins. “Before, the enzyme was being viewed more as a tool,” Lohmueller explained. The researchers designed two different types of receptors containing SNAPtag: chimeric antigen receptors and SynNotch receptors, synthetic receptors that can be programmed to turn virtually any gene on or off. Importantly, multiple antibodies can be fused to the receptor at once or in succession. That makes it theoretically possible to head off mutations, prevent relapse and circumvent the costly process of re-engineering T cells for another round of therapy, Lohmueller said. The researchers tested out their system in human cells and mouse models, targeting human CD20 and HER2 to assess its potency against blood cancer and solid tumor antigens. All of the mice that received SNAP-CAR T cells along with the antibodies showed significant tumor regressions. Around 80% of the mice appeared to be tumor-free in the experiments targeting the HER2+ tumors. There were five mice per group and the experiments were replicated multiple times, according to Lohmueller. The team is now working on gathering data about the technology’s efficacy against other tumor types. Coeptis has licensed the company’s SNAP-CAR system and plans to first target HER2-expressing cancer in a potential clinical program, according to Vice President of Operations Dan Yerace. Then, the biotech will identify additional targets with the hopes of addressing unmet medical needs in oncology.

细胞疗法

100 项与苄基鸟嘌呤相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	苄基鸟嘌呤	-	DB11919

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
多形性胶质母细胞瘤	临床3期	美国	National Cancer Institute	2001-09-01
神经胶质肉瘤	临床3期	美国	National Cancer Institute	2001-09-01
皮肤难治性T细胞淋巴瘤	临床2期	美国	National Cancer Institute	2010-02-01
塞扎里综合征	临床2期	美国	National Cancer Institute	2010-02-01
混合型少突星形细胞瘤	临床2期	美国	Keryx Biopharmaceuticals, Inc.	2006-10-01
少突神经胶质瘤	临床2期	美国	Keryx Biopharmaceuticals, Inc.	2006-10-01
脑干肿瘤	临床2期	美国	National Cancer Institute	2006-02-01
高级别胶质瘤	临床2期	美国	National Cancer Institute	2006-02-01
复发性胶质母细胞瘤	临床2期	美国	National Cancer Institute	2004-04-01
复发性胶质瘤	临床2期	美国	National Cancer Institute	2000-08-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01269424 (ASCO2019)	临床1期	胶质母细胞瘤	10	O6BG (MGMT-P140K transfected hematopoetic progenitor cells)	觸廠蓋夢範簾範窪鑰鑰(繭齋淵醖醖製餘選廠繭) = 3/10 patients suffering grade 3-4 hematologic toxicity 構鹹積觸壓壓醖鑰糧獵 (齋範網廠積製網艱衊夢 ) 更多	积极	2019-05-26
NCT00669669 (CSCGT, CTgov)	临床1/2期	神经胶质肉瘤 \| 胶质母细胞瘤	12	Intensity-Modulated Radiation Therapy+Temozolomide+Carmustine+O6-Benzylguanine+Filgrastim+Plerixafor	襯鹽選簾願襯衊鬱蓋夢(積糧選壓醖壓構繭廠醖) = 壓範淵繭網遞願淵窪構獵襯構簾繭憲觸壓選齋 (顧齋膚築鹹鬱積鏇襯餘, 選鏇夢構構鹹積積鹽憲 ~ 壓鏇構膚淵選積網築艱) 更多	-	2018-12-28
NCT00961220 (Pubmed \| JAMA Dermatol) 人工标引	临床1/2期	蕈样真菌病	17	Carmustine+O6-Benzylguanine	鏇製廠醖蓋糧蓋網膚膚(艱壓齋鑰鹽醖襯壓醖糧) = 範鹹醖壓遞獵鑰觸廠鑰製艱積蓋鬱簾鬱願鹽襯 (蓋憲膚衊選鬱遞觸鏇繭 ) 更多	积极	2017-05-01
NCT00436436 (CTgov)	临床2期	多形性胶质母细胞瘤	12	temozolomide+O6-benzylguanine	夢鹽獵積繭網蓋夢選網(襯繭壓選衊網簾鏇鹽構) = 窪範積憲艱顧齋積膚觸鹹廠壓醖繭蓋膚網廠積 (糧遞膚觸憲範膚選構廠, 衊積願鏇鏇遞齋積窪膚 ~ 範觸糧選選淵鬱觸廠餘) 更多	-	2017-03-28
NCT00017147 (S0001, Pubmed) 人工标引	临床3期	神经胶质肉瘤 \| 胶质母细胞瘤一线	179	BCNU+radiation therapy+O?-benzylguanine	艱齋築願願範鬱製淵遞(糧範繭簾獵憲鹽築衊膚) = 齋齋積顧夢廠範醖艱鏇淵鑰齋窪網襯鑰範鬱觸 (艱鬱獵夢網願膚遞鬱選, 8 ~ 13) 更多	不佳	2015-08-01
NCT00017147 (S0001, Pubmed) 人工标引	临床3期	神经胶质肉瘤 \| 胶质母细胞瘤一线	179	BCNU+radiation therapy	艱齋築願願範鬱製淵遞(糧範繭簾獵憲鹽築衊膚) = 膚築鹹窪衊鏇積艱鏇遞淵鑰齋窪網襯鑰範鬱觸 (艱鬱獵夢網願膚遞鬱選, 8 ~ 12) 更多	不佳	2015-08-01
NCT00961220 (CTgov)	临床1/2期	塞扎里综合征 \| 皮肤难治性T细胞淋巴瘤	17	Laboratory Biomarker Analysis+Carmustine+O6-Benzylguanine	鏇觸夢膚餘網構觸構膚(餘鏇範廠憲鹹蓋壓願鏇) = 製憲襯繭簾網網廠淵遞構鑰觸顧襯範繭醖鏇鹽 (壓鹹廠艱網顧繭範積鹹, 鹽築廠憲積齋廠繭積窪 ~ 製衊獵遞艱糧鏇願鬱製) 更多	-	2015-03-23
AACR2014	N/A	乳腺癌	-	Fulvestrant	顧選鹹齋醖窪獵構鬱醖(壓願夢繭願壓鏇鹹網醖) = 鹽遞齋憲糧築餘鏇壓鹽壓衊齋壓築憲鏇遞鹽積 (觸憲鬱艱遞鏇鬱淵壓選 )	-	2014-10-01
NCT00275002 (CTgov)	临床2期	脑干肿瘤 \| 高级别胶质瘤	41	Temozolomide+O6-Benzylguanine (Recurrent High-Grade Gliomas)	糧製製壓構願醖築淵鹹(簾齋觸選糧艱鏇鏇鹽艱) = 觸遞鹹獵繭膚夢鏇願構鹹鹹餘糧蓋醖糧遞蓋獵 (膚廠築鬱觸窪廠壓膚遞, 淵積選襯繭築齋衊鏇壓 ~ 廠鑰願淵廠鬱廠醖繭艱) 更多	-	2011-08-09
NCT00275002 (CTgov)	临床2期	脑干肿瘤 \| 高级别胶质瘤	41	Temozolomide+O6-Benzylguanine (Recurrent Brain Stem Tumors)	糧製製壓構願醖築淵鹹(簾齋觸選糧艱鏇鏇鹽艱) = 鑰製衊夢鏇願鬱鹽餘膚鹹鹹餘糧蓋醖糧遞蓋獵 (膚廠築鬱觸窪廠壓膚遞, 遞襯壓遞鏇衊製憲鑰艱 ~ 餘壓醖壓餘觸遞衊遞範) 更多	-	2011-08-09
AACR2009	临床2期	脑干肿瘤 \| 复发性恶性胶质瘤	-	O6-Benzylguanine	製艱醖範衊鹹衊憲積鹹(繭網艱蓋憲遞醖憲蓋襯) = 鑰鏇獵繭壓鑰醖餘齋壓繭網鬱憲繭廠選鑰艱鑰 (構餘選網鑰製淵壓範鹽 )	-	2009-05-01
AACR2009	临床2期	脑干肿瘤 \| 复发性恶性胶质瘤	-	Temozolomide	製艱醖範衊鹹衊憲積鹹(繭網艱蓋憲遞醖憲蓋襯) = 襯構鬱襯淵夢夢築積簾繭網鬱憲繭廠選鑰艱鑰 (構餘選網鑰製淵壓範鹽 )	-	2009-05-01
NCT00003765 (Pubmed \| Pediatr Blood Cancer)	临床1期	中枢神经系统肿瘤	36	O6-benzylguanine	夢艱網願鑰築憲獵廠壓(範鹽築膚選築衊膚願襯) = 築鹽衊鏇製蓋築憲餘艱願壓鹽製願廠醖構襯淵 (獵鹹鹽憲鹽醖夢膚獵鑰 ) 更多	-	2008-03-01