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1.
Since the clinical introduction of anti-CD20 monoclonal antibodies into lymphoma treatment, immunologic approaches in lymphoma have made substantial progress. Advances in our understanding of tumor immunology have led to the development of strategies to overcome immunologic barriers responsible for an ineffective immune response. Specifically, therapeutic agents have been developed and tested against molecules that are responsible for T-cell exhaustion. The use of monoclonal antibodies against immune checkpoints in the adaptive immune system, such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, has changed the landscape of cancer therapy including the treatment of lymphoma. This achievement has recently been accompanied by the development of novel immune checkpoint inhibitors targeting the innate immune system, including the CD47-SIRPα signaling pathway, and this approach has yielded promising results. To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells. 相似文献
2.
Summary A semi-quantitative procedure is described for measuring cell viability after short-term exposure to a test substance using
a monolayer culture. Test substances are placed in direct contact with cell monolayers for various time intervals. The substances
are removed and the monolayers are incubated in the presence of fluorescein diacetate. Monolayers are viewed under a fluorescent
microscope and the percentage of fluorescing (viable) cells is estimated. The method is suitable for examining cytotoxic effects
at short times of exposure and for discriminating between test substances that give similar, low toxicity endpoints in standard
24-h assays. 相似文献
3.
Alicia Gómez-Barrio David Montero-Pereira Juan J. Nogal-Ruiz José A. Escario Susana Muelas-Serrano Vladimir V. Kouznetsov Leonor Y. Vargas Méndez Juan M. Urbina Gonzáles Carmen Ochoa 《Acta parasitologica / Witold Stefański Institute of Parasitology, Warszawa, Poland》2006,51(1):73-78
A study of some antiparasitic properties of several homoallylamines and related tetrahydroquinolines and quinolines, previously
described, was carried out using in vitro activity assays against the epimastigote form of Trypanosoma cruzi and against Trichomonas vaginalis. Unspecific cytotoxicity against murine macrophages was also studied. Although the antichagasic and trichomonacidal activities
are not comparable to those of the standard drugs, nifurtimox and metronidazole, some of the compounds exhibit an interesting
specific antiparasitic activity. 相似文献
4.
Arsenic trioxide–loaded, microemulsion-enhanced cytotoxicity on MDAH 2774 ovarian carcinoma cell line 总被引:2,自引:0,他引:2
M.C. TEREK B. KARABULUT† N. SELVI‡ L. AKMAN Y. KARASULU§ I. OZGUNEY§ A.U. SANLI† R. USLU† & A. OZSARAN 《International journal of gynecological cancer》2006,16(2):532-537
The antiproliferative effect of As(2)O(3)-loaded microemulsion (As(2)O(3)-M) on human MDAH 2774 ovarian cancer cells was compared with a regular solution of the As(2)O(3). We used MDAH 2774 as model cell lines for ovarian cancer. The (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) (XTT) and trypane blue dye exclusion tests were used to evaluate cytotoxicity. Apoptotic effect of solutions was evaluated using cell death detection kit. Standard microemulsion formulation used in this experiment contains 5 x 10(-6) M As(2)O(3). It was clearly demonstrated that As(2)O(3)-M had a significant cytotoxic effect on MDAH 2774 cell line, and the cytotoxic effect of As(2)O(3)-M was significantly higher than that of regular As(2)O(3) solutions. Even approximately 6000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As(2)O(3) showed a cytotoxic effect. As a result, this diluted concentration (approximately 8 x 10(-10) M) was found to be approximately 6000 times more effective than regular As(2)O(3) solutions (5 x 10(-6) M). Moreover, this diluted concentration resulted in 1.5-fold enhancement of apoptosis. According to the in vitro cytotoxicity studies, we concluded that by incorporating As(2)O(3) into the microemulsion (As(2)O(3)-M), which is a new drug carrier system, it is possible to increase antiproliferative effect of regular As(2)O(3) on MDAH 2774 cells. Translating these results to in vivo conditions would open new windows in the treatment of ovarian cancer. 相似文献
5.
目的探索可溶性HLAG1分子结构对功能的影响,为其临床应用打下基础。方法通过分子克隆技术,去掉HLAG1重链分子α1功能区氨基端24肽,然后与轻链蛋白在体外与九肽共折叠复性形成复合物,并检测复合物对NK细胞杀伤活性的影响。结果成功构建突变的HLAG1重链分子的原核表达载体,表达的重链蛋白与轻链蛋白形成复合物,经Westernblot鉴定可与HLAⅠ类分子的单抗W6/32结合,并且可明显抑制NK细胞对K562细胞的细胞毒作用。结论α1功能区氨基端缺失24肽的HLAG1分子,可抑制NK细胞的细胞毒作用。 相似文献
6.
5种稀土粉尘的细胞毒性研究 总被引:4,自引:0,他引:4
本研究应用荧光偏振测量技术测定了豚鼠肺泡巨噬细胞膜流动性,用原子吸收分光光度仪测定细胞钾,并通过测定细胞培养液中乳酸脱氢酶的活性、细胞死亡率及扫描电镜观察巨噬细胞形态学变化,研究了CeO_2、包钢混合稀土、硅铁合金、Y_2O_3及富钇5种粉尘对细胞的毒作用。结果表明,5种粉尘对细胞均产生一定毒性,并有明显的剂量-反应关系。经毒性大小比较,CeO_2毒性较轻,接近TiO_2,包钢混合稀土与硅铁合金相近,毒性居中,Y_2O_3和富钇毒性较大,但轻于SiO_2。 相似文献
7.
目的 对长柄梭罗Reevesia longipetiolata树皮具细胞毒活性的醋酸乙酯部分化学成分进行研究。方法 采用常压、加压硅胶柱色谱、Sephadex LH-20凝胶柱色谱、高效液相色谱进行分离和纯化,通过理化和波谱分析方法鉴定化合物结构。结果 从其醋酸乙酯部分分离得到5个化合物,分别鉴定为β-谷甾醇(β-sitosterol,I)、胡萝卜苷(daucosterol,Ⅱ)、白桦脂酸(betulinic acid,Ⅲ)、羽扇豆醇(lupeol,Ⅳ)和( )-儿茶素[( )-catechin,V]。结论 5个化合物均为首次从该属植物中分得,并分别讨论了它们的细胞毒活性。 相似文献
8.
多抗甲素对人NK细胞活性的作用机理研究 总被引:1,自引:0,他引:1
作者应用单细胞细胞毒试验及形态学观察,研究多抗甲素(PAA)对人体自然杀伤(NK)细胞活性的作用机理。结果表明:PAA能增强食道癌患者淋巴细胞(PBL)明显低下的结合率(B%)和杀伤率(K%),也可增强正常人PBL的K%,但对正常人PBL的B%无影响。形态学观察发现:与靶细胞结合的PBL除大颗粒PBL外,尚有普通的非颗粒PBL,结合的靶细胞损伤首先表现为线粒体肿胀、空泡变,然后核固缩,核膜损伤,细胞严重空泡变性等,偶见靶细胞与自然杀伤细胞结合部质膜破损的现象。经PAA预处理的靶效细胞结合的形态改变无明显差异,但食道癌组的杀伤作用出现较早,且明显增强。 相似文献
9.
L H Anderson T L McDonald G M Thiele L W Klassen 《Journal of clinical laboratory analysis》1992,6(3):113-118
Different assay systems have been used to quantitate lymphokine-induced natural cytotoxic activity as a measure of immune status. This study compares the effects of inducing cytotoxicity in a bulk culture system, where effector cells are transferred to a micro culture well for assay, to a micro culture system where the effector cells are not transferred. The effector/target ratio for both the bulk and micro culture systems was calculated using the number of viable effector cells present at the time of target cell addition. After overnight incubation with interleukin-2 (IL-2), the lytic activity of murine spleen cells to targets using a micro culture system was increased two-fold over the bulk culture method. This increase was amplified further after 5 days of activation with IL-2, in that the micro culture system resulted in a four-fold increase in cytotoxic activity. The loss of some adherent cells in the bulk culture system did not explain the overall decrease in recovered cytotoxicity. The difference appeared to be related to cell loss during centrifugation. Therefore, the E/T ratios are different in the two systems if not corrected for the number of viable cells. 相似文献
10.
肿瘤浸润性淋巴细胞(TIL)经白细胞介素2(IL-2)体外培养后具有很强的体内外抗肿瘤作用,且有一定的靶细胞特异性,其抗肿瘤效果强于淋巴因子激活的杀伤细胞即LAK细胞(P<0.01)。从瘤体中新鲜分离到的TIL对自体肿瘤细胞的杀伤活性极低,经IL-2体外培养后,其杀伤活性逐渐增高,以培养至7~25d的杀伤活性最强,这与IL-2使TIL分泌3种抗癌淋巴因子包括IL-2、IFN-γ、淋巴毒素(LT)增加有关。体外培养25d后,TIL的抗肿瘤活性下降,实验表明这与培养过程中TIL的Lyt-2~+细胞(Tc)减少而L3T4~+细胞(T_H)增多有关。TIL经冻存复苏和IL-2体外培养后仍保持很强的抗肿瘤活性,冻存前后比较未见显著差异(P>0.05),这为间断地运用TIL治疗复发性、晚期肿瘤提供了一条可行的途径。 相似文献