Proangiogene und Tumor fördernde Eigenschaften des Nerve Growth Factor auf murine Lungenkarzinome in vitro

Pneumologie ◽  
2010 ◽  
Vol 64 (01) ◽  
Author(s):  
KM Seidler ◽  
H Renz ◽  
WA Nockher
Author(s):  
Ф.М. Шакова ◽  
Т.И. Калинина ◽  
М.В. Гуляев ◽  
Г.А. Романова

Цель исследования - изучение влияния комбинированной терапии (мутантные молекулы эритропоэтина (EPO) и дипептидный миметик фактора роста нервов ГК-2H) на воспроизведение условного рефлекса пассивного избегания (УРПИ) и объем поражения коры мозга у крыс с двусторонним ишемическим повреждением префронтальной коры. Методика. Мутантные молекулы EPO (MЕРО-TR и MЕPО-Fc) с значительно редуцированной эритропоэтической и выраженной цитопротекторной активностью созданы методом генной инженерии. Используемый миметик фактора роста нервов человека, эндогенного регуляторного белка, в экспериментах in vitro проявлял отчетливые нейропротективные свойства. Двустороннюю фокальную ишемию префронтальной коры головного мозга крыс создавали методом фотохимического тромбоза. Выработку и оценку УРПИ проводили по стандартной методике. Объем повреждения мозга оценивался при помощи МРТ. MEPO-TR и MEPO-Fc (50 мкг/кг) вводили интраназально однократно через 1 ч после фототромбоза, ГК-2Н (1 мг/кг) - внутрибрюшинно через 4 ч после фототромбоза и далее в течение 4 послеоперационных суток. Результаты. Выявлено статистически значимое сохранение выработанного до ишемии УРПИ, а также значимое снижение объема повреждения коры при комплексной терапии. Полученные данные свидетельствуют об антиамнестическом и нейропротекторном эффектах примененной комбинированной терапии, которые наиболее отчетливо выражены в дозах: МEPO-Fc (50 мкг/кг) и ГК-2Н (1 мг/кг). Заключение. Подтвержден нейропротекторный эффект и усиление антиамнестического эффекта при сочетанном применении мутантных производных эритропоэтина - MEPO-TR и MEPO-Fc и дипептидного миметика фактора роста нервов человека ГК-2H. The aim of this study was to investigate the effect of combination therapy, including mutant erythropoietin molecules (EPO) and a dipeptide mimetic of the nerve growth factor, GK-2H, on the conditioned passive avoidance (PA) reflex and the volume of injury induced by bilateral ischemia of the prefrontal cortex in rats. Using the method of genetic engineering the mutant molecules of EPO, MERO-TR and MEPO-Fc, with strongly reduced erythropoietic and pronounced cytoprotective activity were created. The used human nerve growth factor mimetic, an endogenous regulatory protein based on the b-bend of loop 4, which is a dimeric substituted dipeptide of bis- (N-monosuccinyl-glycyl-lysine) hexamethylenediamine, GK-2 human (GK-2H), has proven neuroprotective in in vitro experiments. Methods. Bilateral focal ischemic infarction was modeled in the rat prefrontal cortex by photochemically induced thrombosis. The PA test was performed according to a standard method. Volume of brain injury was estimated using MRI. MEPO-TR, and MEPO-Fc (50 mg/kg, intranasally) were administered once, one hour after the injury. GK-2Н (1 mg/kg, i.p.) was injected four hours after the injury and then for next four days. Results. The study showed that the complex therapy provided statistically significant retention of the PA reflex developed prior to ischemia and a significant decrease in the volume of injury. The anti-amnestic and neuroprotective effects of combination therapy were most pronounced at doses of MEPO-Fc 50 mg/kg and GK-2H 1 mg/kg. Conclusion. This study has confirmed the neuroprotective effect and enhancement of the anti-amnestic effect exerted by the combination of mutant erythropoietin derivatives, MEPO-TR and MEPO-Fc, and the dipeptide mimetic of human growth factor GK-2H.


2014 ◽  
Vol 22 ◽  
pp. S35
Author(s):  
C. Driscoll ◽  
A. Chanalaris ◽  
C. Knight ◽  
C. Gentry ◽  
S. Bevan ◽  
...  

Development ◽  
1970 ◽  
Vol 24 (2) ◽  
pp. 381-392
Author(s):  
Peddrick Weis

The effect of the nerve growth factor (NGF) on chick embryo spinal ganglia was studied in the hanging-drop bioassay system by comparison with parallel development in vivo. The well-differentiated ventrolateral neuroblasts, which in vivo increase 1·33 times in size during the culture period, did not increase in size at all in vitro. Only 65–72% survived to the end of the culture period regardless of the NGF concentration. The less-differentiated mediodorsal (M-D) neuroblasts, which in vivo increase 1·31 times in size during the culture period, were found to increase equally in vitro if sufficient NGF was present. Such a quantity was greater than that which evoked maximum outgrowth of neurites. Survival of M-D neuroblasts was also related to NGF concentration but did not equal the in vivo condition even at the highest concentration. The hyperchromatic type of degeneration prevented by high NGF concentrations is that which results in vivo from insufficient peripheral field. From this and other reports it would appear that the response to NGF seen in vitro is due only to the M-D neuroblasts, and that all biochemical and cytological observations which have been reported would therefore represent conditions within those cells only.


1991 ◽  
Vol 11 (9) ◽  
pp. 4635-4641 ◽  
Author(s):  
J E Green

Three lines of transgenic mice containing the human T-cell lymphotropic virus type I (HTLV-I) tax gene develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1327, 1987). Tumors and tumor cell lines derived from these mice produce neurite outgrowth from PC-12 cells and nerve growth factor (NGF), as determined by RNA (Northern) blot analysis and enzyme-linked immunosorbent assays. In vitro cotransfection studies demonstrate that Tax is able to trans activate the NGF promoter in NIH 3T3 fibroblast cells. The major cis-acting tax-responsive element in the NGF promoter (AGGGTGTGACGA) has 92% homology with a tax-responsive element contained within the 21-bp repeats of the HTLV-I long terminal repeat. The receptor for NGF is also expressed in the transgenic tumor cells, suggesting that Tax may activate an autocrine mechanism through the upregulation of NGF.


2016 ◽  
Vol 32 (2) ◽  
pp. 146-162 ◽  
Author(s):  
Haixing Xu ◽  
Lingxi Zhang ◽  
Yun Bao ◽  
Xiumei Yan ◽  
Yixia Yin ◽  
...  

The usage of hollow nerve conduits shows inferior recovery effect on the repair of peripheral nerve defects. In this study, a biocompatible and biodegradable pH-induced injectable chitosan–hyaluronic acid hydrogel for nerve growth factor encapsulation and sustained release was developed as the fillers in the lumen of hollow nerve conduit to reform its microenvironment for peripheral nerve regeneration. The physicochemical properties of hydrogel were characterized by gelation time, Fourier transform infrared spectroscopy, scanning electron microscopy, compressive modulus, porosity, swelling ratio, and in vitro degradation. The in vitro nerve growth factor release profiles and cell evaluation were also investigated. The results show that the structure of chitosan–hyaluronic acid hydrogel is composed of interconnected channels with a controllable pore diameter ranging from 20 to 100 µm. The hydrogel can be degraded more than 70% within 8 weeks in vitro and is available for nerve growth factor sustained release. The chitosan–hyaluronic acid/nerve growth factor hydrogel is non-toxic and suitable for adhesion and proliferation of nerve cells and capable of maintaining nerve growth factor activity. Therefore, it could be a promising intraluminal filler of nerve conduits for peripheral nerve regeneration in neural tissue engineering.


Sign in / Sign up

Export Citation Format

Share Document