| Part1:The suppressive effect of two subtypes of ndrg2 on the human glioma in vivoCancer is the most deadly disease in human beings. The exploration of antitumor gene drugs is the most important task in the 21st century. Glioma is the most common tumor in the central nervous system. The main therapeutic methods are surgery, chemotherapy and radiotherapy. The five-year survival rate is very low. As a result, it's urgent to explore therapeutic biomedicine to treat glioma.NDRG2 was discovered and cloned by Deng yanchun using polymerase chain reaction-based subtractive hybridization from glioblastoma. The gene is 2024bp in length, consisting 16 exons and 15 introns. It has two subtypes, ndrg2L and ndrg2S, encoding 371 and 357 amino acids respectively. In adult tissues, the highest expression level was found in the salivary glands, various neural tissues and skeletal muscles and was nearly undetectable in the thymus, bone marrow, testis and peripheral blood leukocyte. This expression pattern suggests an inverse correlation between the level of ndrg2 gene expression and the rate of cell proliferation. In vitro studies revealed that ndrg2 had suppressive effect on more than 20 cell lines such as glioma, lung cancer and gastric cancer.Our research group had successfully established the two variants of recombinant adenovirus vectors: pAd-CMV/V5-DEST-ndrg2L and pAd-CMV/V5-DEST-ndrg2S. And we initially proved the anti-glioma effect of the vectors in vitro. To explore the anti-tumor effect and the effective dose in vivo , and to compare the differences between the two subtypes of ndrg2 , we conducted the experiments of the primary pharmacology of the recombinant adenovirus vector.We first amplified and purified a certain amount of the recombinant adenovirus vector: pAd-CMV/V5-DEST-ndrg2L and pAd-CMV/V5-DEST- ndrg2S. Western blotting test proved that the recombinant adenovirus can express the ndrg2 protein correctly. The virus titer was 5×109IU/ml.Then we established the nude mice model of human glioma subcutaneous transplantation. When the tumor grew to about 5mm, we injected the recombinant adenovirus into the tumor and observed the tumor growth. Then we depicted the growth curve. The results revealed that the two subtypes of ndrg2 recombinant adenovirus inhibited the tumor growth in a certain degree compared to the control group, though not obviously. In addition, the differences between the efficacies of the two subtypes were not obvious. In the experiment of multiple dose administration of ndrg2s, the anti-tumor effective of high dose group(2×109IU/ml) was stronger than medium dose(2×108IU/ml) and low dose group(2×107IU/ml).Part2::The effectiveness and tolerability of levetiracetam as adjunctive therapy for refractory epilepsyEpilepsy is a disease caused by the synchronized and limited paradoxical discharge with known or unknown causes. It is characterized by recurrent, transient and stereotyped functional disorder of central nervous system. Antiepileptic drugs are the most important treatment of epilepsy. Most of the seizures can be well controlled using the first line AEDs while 20%-30% patients develop to refractory epilepsy which remains an unsolved clinical problem. Lots of treatments are under exploration. The use of AEDs is still an important method of treating refractory epilepsy. As a result of the drug resistance to most AEDs in refractory epilepsy, the application of optimal combinations of drugs and the use of new AEDs are becoming the main strategies of treating refractory epilepsy.Levetiracetam is a new AED used in the US and Europe for many years. It is approved in 2007 in China. Unlike other traditional AEDs which act on the ion channels or activate the Inhibitory Neurotransmitter system, it produces its effect by binding to synaptic vesicle protein 2A (SV2A), an integral membrane protein located on synaptic vesicles. Overseas research had revealed that LEV appeared to be a safe and effective drug in treating refractory epilepsy. However, the efficacy and safety of LEV need to be evaluated in China. As a result, we evaluated the efficacy and safety of LEV as an adjunctive therapy for refractory epilepsy retrospectively to provide some evidence of the drug application . Retrospective case note review of 35 patients with refractory epilepsy who received treatment with levetiracetam and were followed up for 3 months to 18 months. 48.5% patients had more than 50% reduction in seizure frequency, and the difference of efficacy between focal and generalized epilepsy was not statistically significant. The 12 months retention rate was 42.8%. 31.5% patients reported one or more adverse effects, but no serious adverse effect appeared. LEV proved to be an effective and safe treatment in patients with refractory seizures and can be an add-on treatment for refractory seizures. |
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