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排序方式: 共有852条查询结果,搜索用时 15 毫秒
1.
《Bioorganic & medicinal chemistry》2019,27(15):3279-3284
Photodynamic therapy (PDT) is a treatment method using light and photosensitizers (PSs), which is categorized as a non-invasive surgery treatment for cancers. When the tumor is exposed to a specific light, the PSs become active and generate reactive oxygen species (ROS), mainly singlet oxygen which kills nearby cancer cells. PDT is becoming more widely recognized as a valuable treatment option for localized cancers and pre-cancers of skin as it has no long-term effects on the patient. But, due to the limited penetration rate of light into the skin and other organs, PDT can’t be used to treat large cancer cells or cancer cells that have grown deeply into the skin or other organs. Hence, in this study, our focus centers on synthesizing glucose-conjugated phthalocyanine (Pc) compatible with near-infrared (NIR) irradiation as second-generation photosensitizer, so that PDT can be used in a wider range to treat cancers without obstacles. 相似文献
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《Bioorganic & medicinal chemistry》2016,24(22):6040-6047
A series of β-alkylaminoporphyrins conjugated with different amines at β position (D1–D3) or with electron-donating and electron-withdrawing substituents at phenyl position (D4–D6) were synthesized. Their photophysical and photochemical properties, intracellular localization, photocytotoxicities in vitro and vivo were also investigated. All target compounds exhibited no cytotoxicities in the dark and excellent photocytotoxicities against HeLa cells. Among them, D6 showed the highest phototoxicity and the lowest dark toxicity, which was more phototoxic than Hematoporphyrin monomethyl ether (HMME). In addition, D6 exhibited best photodynamic antitumor efficacy on BALB/c nude mice bearing HeLa tumor. Therefore, D6 is a powerful and promising antitumor photosensitizer for photodynamic therapy. 相似文献
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Mikael Dohlsten Peter A. Lando Per Björk Lars Abrahmsén Lennart Ohlsson Peter Lind Terje Kalland 《Cancer immunology, immunotherapy : CII》1995,41(3):162-168
T lymphocytes generally fail to recognize human colon carcinomas, suggesting that the tumour is beyond reach of immunotherapy. Bacterial superantigens are the most potent known activators of human T lymphocytes and induce T cell cytotoxicity and cytokine production. In order to develop a T-cell-based therapy for colon cancer, the superantigen staphylococcal enterotoxin A (SEA) was given tumour reactivity by genetic fusion with a Fab fragment of the monoclonal antibody C242 reacting with human colon carcinomas. The C242Fab-SEA fusion protein targeted SEA-reactive T cells against MHC-class-II-negative human colon carcinoma cells in vitro at nanomolar concentrations. Treatment of disseminated human colon carcinomas growing in humanized SCID mice resulted in marked inhibition of tumour growth and the apparent cure of the animals. Therapeutic efficiency was dependent on the tumour specificity of the fusion protein and human T cells. Immunohistochemistry demonstrated massive infiltration of human T cells in C242Fab-SEA-treated tumours. The results merit further evaluation of C242Fab-SEA fusion proteins as immunotherapy in patients suffering from colon carcinoma. 相似文献
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Asano R Ikoma K Shimomura I Taki S Nakanishi T Umetsu M Kumagai I 《The Journal of biological chemistry》2011,286(3):1812-1818
Diabodies (Dbs) and tandem single-chain variable fragments (taFv) are the most widely used recombinant formats for constructing small bispecific antibodies. However, only a few studies have compared these formats, and none have discussed their binding kinetics and cross-linking ability. We previously reported the usefulness for cancer immunotherapy of a humanized bispecific Db (hEx3-Db) and its single-chain format (hEx3-scDb) that target epidermal growth factor receptor and CD3. Here, we converted hEx3-Db into a taFv format to investigate how format affects the function of a small bispecific antibody; our investigation included a cytotoxicity assay, surface plasmon resonance spectroscopy, thermodynamic analysis, and flow cytometry. The prepared taFv (hEx3-taFv) showed an enhanced cytotoxicity, which may be attributable to a structural superiority to the diabody format in cross-linking target cells but not to differences in the binding affinities of the formats. Comparable cross-linking ability for soluble antigens was observed among hEx3-Db, hEx3-scDb, and hEx3-taFv with surface plasmon resonance spectroscopy. Furthermore, drastic increases in cytotoxicity were found in the dimeric form of hEx3-taFv, especially when the two hEx3-taFv were covalently linked. Our results show that converting the format of small bispecific antibodies can improve their function. In particular, for small bispecific antibodies that target tumor and immune cells, a functional orientation that avoids steric hindrance in cross-linking two target cells may be important in enhancing the growth inhibition effect. 相似文献
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自从二十世纪五十年代开始认识腺病毒(Adenovirus)以来,对腺病毒的生物学和免疫学特征已经有比较多的认识。腺病毒科包括禽腺病毒属(Aviadenovius)和哺乳动物腺病毒(Mastadenov irus)两个属。除人腺病毒以外,一些哺乳动物的腺病毒和禽腺病毒也成为基因治疗和载体疫苗研究的热点,如猪腺病毒3型(PAV-3)、牛腺病毒3型(BAV-3)、绵羊腺病毒(Ovine adenovirus,OAV)、禽腺病毒(Aviadenovirus)、犬腺病毒(Canine adeno virus,CAV)和黑猩猩腺病毒(Chimpanzee adenovirus)。不同种属的腺病毒虽然基因组序列完全不同,但其结构和功能却非常相似,而且各型腺病毒之间很少有交叉免疫反应,这就为利用这些腺病毒研制基因治疗载体和活载体疫苗提供了丰富的材料。近年来的研究也发现,如果利用一种腺病毒载体来进行重复免疫,宿主针对腺病毒载体蛋白的免疫反应比较强大,造成转基因表达时间缩短,重复免疫的效果较差,换用不同的病毒载体,则可以回避这种免疫反应,提高转基因的表达时间和保护性免疫反应。腺病毒可以感染很多分裂期或静止期细胞,即使在一些高度分化的组织细胞中也可增殖,如可有效的感染肌肉组织、心、肺和脑组织,并能高效的复制、表达其基因产物,因此腺病毒成为基因治疗和活病毒载体疫苗研究的首选工具。 相似文献
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健脾化瘀中药提高胞嘧啶脱氨酶/单纯疱疹病毒胸苷激酶基因治疗肝细胞癌的实验研究 总被引:2,自引:0,他引:2
目的:观察健脾化瘀中药提高胞嘧啶脱氨酶/单纯疱疹病毒胸苷激酶基因治疗肝细胞癌的作用。方法:脂质体lipofectamine将含有双自杀基因的腺病毒载体pAd-CD/TK导人293细胞,收集病毒上清转染人肝癌细胞BEL7402,MTT法测定BEL7402细胞存活率。裸鼠人肝癌模型转染CD/TK双自杀基因后,给予5-FC500mg/kg,GCV 100mg/kg腹腔注射,同时予健脾化瘀中药960复方灌胃。观察肿瘤生长情况。结果:给予前体药物5-FC和GCV后,CD/TK转染细胞被杀死。并表现出较强的旁观者效应。转染细胞比例达到10%即表现出较强的杀伤作用(P<0.01)。健脾化瘀中药960复方具有提高旁观者效应作用,1.67ml/kg和2.5ml/kg960复方含药血清组细胞存活率显著低于对照组(P<0.01)。转染基因组应用5-FC和GCV治疗后,裸鼠肝癌的生长明显受到抑制(P<0.05),抑瘤率39.42%,单用中药组抑瘤率18.04%,中药与CD/TK 5-FC/GCV联合运用组,较单纯CD/5-FC/HSV-tk/GCV对裸鼠肿瘤模型的生长抑制作用更加明显(P<0.05),抑瘤率55.10%。结伦:腺病毒介导CD/TK自杀基因可有效地杀死人肝癌BEL7402细胞,健脾化瘀中药960复方具有显著提高CD/TK双自杀基因对人肝癌细胞的抑杀作用。 相似文献
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成纤维细胞生长因子(FGFs)通过作用于其受体(成纤维细胞生长因子受体,FGFRs)在许多生理过程中发挥重要作用,如胚胎形成、创伤修复、血管生成等。近年来,越来越多的证据表明FGFRs是某些癌症的驱动基因,并且以"细胞自治"的方式维持肿瘤细胞的恶性特征,通过诱导促有丝分裂和生存信号、促进肿瘤细胞侵袭转移、促进上皮间质转化、促进血管生成及参与肿瘤复发耐药作用作为癌基因参与肿瘤发生发展进程的多重步骤,但也有研究证实FGFR信号在某些肿瘤类型中具有抑制肿瘤的功能。这些研究结果使得FGFRs成为越来越具有吸引力的癌症治疗新靶点。本文阐述了FGFRs信号通路在多种肿瘤中的作用,并且对处于研发或试验阶段的抗FGFRs药物(包括小分子酪氨酸激酶抑制剂和单克隆抗体)进行了概括。 相似文献