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11.
Targeting of cytokines into the tumor microenvironment using antibody-cytokine fusion proteins, called immunocytokines, represents
a novel approach in cancer immunotherapy. This article summarizes therapeutic efficacy and immune mechanisms involved in targeting
interleukin-2 (IL-2) to neuroectodermal, tumors using ganglioside GD2-specific antibody-IL-2 fusion protein (ch14.18-IL-2).
Treatment of established melanoma metastases with ch14.18-IL-2 resulted in eradication of disease followed by a vaccination
effect protecting mice from lethal challenges, with wild-type tumor calls. In a syngeneic neuroblastoma model, targeted IL-2
was effective in the amplification of a weak memory immune response previously induced by IL-12 gene therapy using an engineered
linear version of this heterodimeric cytokine. These findings show that targeted IL-2 may provide an effective tool in cancer
immunotherapy and establish the missing link between T cell-mediated, vaccination and objective clinical responses. 相似文献
12.
M. Toselli Patrizia Tosetti Vanni Taglietti 《Pflügers Archiv : European journal of physiology》1997,433(5):587-596
Ca2+ channel modulation by the μ opioid agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAGO) and the δ opiate agonists [d-Pen2, d-Pen5]-enkephalin (DPDPE) and [d-Ala2, d-Leu5]-enkephalin (DADLE) in cultured human neuroblastoma SH-SY5Y cells was investigated using the whole-cell variant of the patch-clamp
technique. In SH-SY5Y cells, differentiated in vitro with retinoic acid, all agonists reversibly decreased high-voltage-activated,
ω-conotoxin-sensitive Ba2+ currents in a concentration-dependent way. Inhibition was maximal with a 1 μM concentration of opiate agonists (76% with DAGO
and 63% with δ agonists, when measured at 0 mV) and was characterized by a clear slow down of Ba2+ current activation at low test potentials. Both inhibition and slow down of activation were attenuated at more positive potentials,
and could be partially relieved by strong conditioning depolarizations. Current suppression operated by both μ and δ agonists
was prevented by pre-treatment of the cells with pertussis toxin. No sign of additivity was observed when δ agonists were
applied to cells that were maximally activated by DAGO, suggesting that a common mechanism, involving the same type of modulating
molecule, is responsible for Ca2+ channel inhibition promoted by activation of μ and δ opioid receptors in SH-SY5Y cells.
Received: 10 October 1996 / Received after revision and accepted: 18 November 1996 相似文献
13.
目的:探讨两价阳离子和针对整合素α2的 特异性阻断性单克隆抗体对神经母细胞瘤细胞株SK-N-SH细胞粘附于胶原蛋白(Col)的影响,探讨整合素α2β1对该细胞粘附反应的调节作用。方法:将含有不同M g2+、Ca2+浓度和有或无抗α2单克隆抗体6F1的SK-N-SH细胞混悬液。加入96孔 平底非细胞培养板,此反应板已包被Ⅰ型大鼠尾Col(4 μg/well),所粘附的细胞用BCA方 法测定,以吸光度(A570)代表粘附细胞的数量。结果:Mg 2+能明显增加SK-N-SH细胞Ⅰ型Col的粘附反应;Mg2+浓度为1 mmol/L时,细胞 粘附的反应已接近高峰,与对照组相比A570分别为0.59±0.03和0.2 5±0.0 1 (P<0.01),而Ca2+对细胞的粘附无明显影响;抗α2单克隆抗体6F1(10 mL /L)能显著阻断SK-N-SH细胞粘附于胶原蛋白(A=0.27±0.01),其粘附水平接近无Mg 2+的粘附反应水平(A=0.32±0.01)。 结论:整合素α2介导 SK-N-SH细胞对胶原蛋白粘附反应,提示整合素α2可能参与调节神经母细胞瘤的转移。 相似文献
14.
Susanne Ott Tommaso Costa Albert Herz 《Naunyn-Schmiedeberg's archives of pharmacology》1986,334(4):444-451
Summary Equilibrium binding isotherms of [3H]diprenorphine in membranes from NG 108-15 cells are consistent with a homogenous population of binding sites. Upon addition of Na+, Mg2+ and GTP, only a 2-fold reduction in affinity with a minor decrease in the number of sites is observed. Dissociation curves of [3H]diprenorphine, however, are clearly biphasic: in the absence of Na+, Mg2+ and GTP, 80% of the bound ligand dissociates slowly with at
1/2 of 100 min, and only 20% rapidly (t
1/2 4.5 min). In the presence of Mg2+, nearly all the binding is found in the slowly dissociating form. Upon the addition of either Na+ or GTP, 20–30% of the binding dissociates more rapidly. The rate constant of the rapidly dissociating form generated by Na+, however, is 2.5 times greater than that induced by the presence of GTP. Thus, the addition of both, Na+ and GTP, converts about 80% of the receptor into a very fast dissociating form (t
1/2 1.7 min).Exposure of intact cells to pertussis toxin (10 ng/ml) or treatment of membranes with N-ethyl maleimide (500 M), strongly reduces the proportion of the slowly dissociating component. Following these treatments, the effect of GTP is reduced or abolished, but that of Na+ remains unaffected.We conclude from these data that the effects of Na+ and GTP are not only distinct in site but also in mechanism of action and that there are three forms of opioid receptors that can be differentiated by their kinetic properties. The slowly dissociating receptor form requires a functional N unit. 相似文献
15.
Dr. Delmar R. Aitken MD G. Alan Hopkins BS John O. Archambeau MD Donald C. Moores MD Douglas A. Weeks MD Antranik A. Bedros MD H. Gibbs Andrews MD James W. Smith MD 《Annals of surgical oncology》1995,2(4):343-350
Background: External beam radiotherapy in advanced neuroblastoma is limited by the volume of normal radiosensitive tissues included in the radiation field. Limitations to external radiation are the late effects to these tissues. Intraoperative radiotherapy (IORT) delivers a single high-radiation dose to a tumor while displacing normal tissues that would have been included in an external field. Standard external radiotherapy can still be done after boost IORT.
Methods: Eight advanced-stage neuroblastoma patients who received IORT as part of their multimodality therapy were reviewed to identify the impact of IORT on operative time, complications, and tumor control in the treatment field. The IORT was accomplished by patient transport from the OR to the radiation therapy suite; these were separated by three floors.
Results: IORT added 30–75 min to the operative procedure. Tumors in the resection/IORT fields showed no evidence of disease (one), stable tumor size (six), and tumor recurrence (one). Two complications were identified: a urinary fistula and CO2 retention, which was detected and corrected before the IORT. Neither of these complications was related to the IORT. Two patients who had subsequent tumor resection after IORT demonstrated tumor differentiation to ganglioneuromatous tissue.
Conclusions: IORT usually can be completed in less than an hour. No IORT-associated complications were identified. IORT along with maximal tumor resection, external radiation, and chemotherapy enhances local tumor control.Presented in part at the 47th Annual Symposium of The Society of Surgical Oncology, Houston, TX, March 17–20, 1994. 相似文献
16.
Philippe Béhé Katrin Sandmeier Hans Meves 《Pflügers Archiv : European journal of physiology》1992,422(2):120-128
The M current, I
M, a voltage-dependent non-inactivating K+ current, was recorded in NG108-15 neuroblastoma × glioma hybrid cells, using the whole-cell mode of the patch-clamp technique. We studied the effect of arachidonic acid, other fatty acids and inhibitors of the arachidonic acid metabolism. In relatively high concentrations (25–50 M) arachidonic acid first increased and later decreased the current, I
h, which holds the membrane potential at –30 mV and mainly flows through open M channels. It shifted the midpoint potential, V
o, of the relation between M conductance, g
M, and membrane potential, V, to more negative values and decreased the maximum conductance ¯g
M and the time constant
M. In smaller concentrations (5–10 M) arachidonic acid merely decreased I
h and ¯g
M with little effect on V
o and
M. Eicosatetraynoic acid and docosa-hexaenoic acid acted similarly to arachidonic acid whereas stearic acid had no effect. Of the three enzyme inhibitors studied, nordihydroguaiaretic acid acted similarly to arachidonic acid. i. e. caused a biphasic change in I
h. Indomethacin and quinacrine caused, respectively, a pure increase and a pure decrease of I
h and ¯g
M. Possible explanations are build-up of internally produced arachidonic acid, depletion of eicosanoid products or an inhibitory effect unrelated to arachidonic acid metabolism. 相似文献
17.
三氧化二砷对神经母细胞瘤细胞增殖的影响 总被引:13,自引:1,他引:13
目的探讨三氧化二砷(As2O3)对儿童神经母细胞瘤有无潜在的治疗价值及伍用细胞因子有无增强疗效的作用。方法应用四甲基偶氮唑蓝法于体外观察As2O3对神经母细胞瘤细胞株SJ-N-SH增殖的影响;并观察As2O3伍用重组人γ-干扰素、肿瘤坏死因子、白细胞介素4、6、10后的情况。结果0.5~4μmol/L的三氧化二砷明显抑制SJ-N-SH细胞的增殖,As2O3伍用γ-干扰素、白细胞介素4可明显增强As2O3对SJ-N-SH细胞增殖的抑制,而其他几种细胞因子无明显作用。结论As2O3为治疗神经母细胞瘤的有效药物,联合应用合适的细胞因子可增强As2O3的疗效。 相似文献
18.
A case of adrenal cystic neuroblastoma (NB) detected by prenatal ultrasonography (US) is presented. The suprarenal mass initially
showed pure cystic features on a variety of imaging studies such as US, computed tomography, and magnetic resonance imaging.
Tumor markers were negative. The mass was suspected to be an adrenal hemorrhage rather than a NB. Three months later, although
the diameter was unchanged, the thickness of the cyst wall seemed to have slightly increased. Surgical exploration revealed
an adrenal cystic tumor and histology showed a NB in situ. Forty-five infants with prenatally detected NB were found in the
English literature; about one-half of them were cystic NBs, and most had a favorable outcome.
Accepted: 29 July 1996 相似文献
19.
目的:探讨儿童胚细胞起源的恶性肿瘤的发生与IGF2和H19基因胚胎印迹缺失(LOI)的关系及肿瘤时这两个基因之间的协同关系。方法:通过PCR-RFLP法和Northernblot法检测包括6例肾母细胞瘤、2例神经母细胞瘤和2例内胚窦瘤在内的10例儿童胚细胞起源的恶性肿瘤中IGF2和H19基因的LOI及H19基因的mRNA表达。结果:①三种肿瘤中均可检测到频发的IGF2基因的LOI,H19基因的LOI相对少见;②肾母细胞瘤中发生IGF2基因LOI的病例全部伴有H19基因mRNA的低水平表达。结论:IGF2基因的LOI与儿童胚细胞起源的恶性肿瘤的发生有密切关系,而这两个基因的相互协同作用可能是肾母细胞瘤发病的重要因素之一。 相似文献
20.
神经母细胞瘤血管内皮细胞生长因子、Ki-67抗原表达及微血管密度研究 总被引:1,自引:0,他引:1
目的 探讨血管内皮细胞生长因子(VEGF)、瘤内微血管密度(MVD)与神经母细胞瘤(NB)细胞增殖及预后的关系。方法 采用S-P免疫组化法,检测VEGF、CD34和Ki-67抗原在21例NB中的表达及MVD计数。结果 VEGF及Ki-67表达与NB病理分型及核分裂指数有关(P〈0.05或P〈0.01),而与NB分化与否、肿瘤大小及性别无关。MVD值在临床各病理参数间差异无显著意义。VEGF表达与MVD值、VEGF与Ki-67表达呈明显正相关(P〈0.01)。结论 VEGF、Ki-67表达与NB细胞增殖及预后密切相关。 相似文献